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Nutrients, Volume 16, Issue 14 (July-2 2024) – 202 articles

Cover Story (view full-size image): In MASLD mouse models, oversupplying dietary fat and sugar has a more lipogenic effect than either nutrient alone. By quantifying the sources of hepatic glycogen and triglyceride synthesis, including the contribution of dietary fructose to these products, our study provides new insights into the interaction of dietary fat with sugar in promoting MASLD. In this study, postprandial hepatic glycogen repletion was not affected by different lipogenic diets. However, the sources of glycogen synthesis were highly influenced by dietary fat and sugar composition, with dietary fructose being a key precursor. Furthermore, a combination of high fat and sugar feeding was the most potent effector of hepatic steatosis. DNL did not contribute a significant fraction of liver TG, but DNL fractional synthesis rates were linked to increased liver TG levels. View this paper
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16 pages, 11002 KiB  
Review
Influence of Intravenous Magnesium Sulfate Infusion on the Subjective Postoperative Quality of Recovery: A Meta-Analysis of Randomized Controlled Trials
by Kuo-Chuan Hung, Li-Chen Chang, Chun-Ning Ho, Chih-Wei Hsu, Jheng-Yan Wu, Yao-Tsung Lin and I-Wen Chen
Nutrients 2024, 16(14), 2375; https://doi.org/10.3390/nu16142375 (registering DOI) - 22 Jul 2024
Abstract
This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly [...] Read more.
This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly improved the global QoR score on postoperative day 1 (standardized mean difference [SMD]: 1.24; 95% confidence interval: 0.70—1.78; p < 0.00001). It also enhanced specific QoR dimensions, with substantial effects on pain (SMD: 1, p < 0.00001) and physical comfort (SMD: 0.85, p < 0.0001), a moderate effect on emotional state (SMD: 0.65, p = 0.002), and small improvements in physical independence (SMD: 0.43, p < 0.00001) and psychological support (SMD: 0.37, p < 0.0001). In addition, magnesium sulfate reduced the intraoperative opioid consumption (SMD: −0.66, p < 0.0001), postoperative pain severity, and the incidence of postoperative nausea and vomiting (risk ratio: 0.48, p = 0.008). The extubation times were unaffected, whereas the post-anesthesia care unit stay was slightly prolonged. These findings highlight the potential of magnesium sulfate as a valuable adjunct for multimodal analgesia and enhanced recovery. Future studies should aim to elucidate the optimal dosing strategies, timing of administration, and specific surgical populations that may derive maximum benefits. Full article
(This article belongs to the Special Issue Magnesium Homeostasis and Magnesium Transporters in Human Health)
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<p>Flowchart of the study selection process.</p>
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<p>Risk of bias assessment [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. D1: bias arising from the randomization process; D2: bias due to deviations from the intended interventions; D3: bias due to missing outcome data; D4: bias in the measurement of the outcome; and D5: bias in the selection of the reported results. Green with Plus Sign (+): Indicates a low risk of bias; Yellow with Question Mark (?): Indicates some concerns regarding the risk of bias.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the quality of recovery (QoR) on postoperative day (POD) 1 [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the pain dimension on postoperative day (POD) 1 [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the physical comfort dimension on postoperative day (POD) 1 [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the emotional dimension on postoperative day (POD) 1 [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the physical independence dimension on postoperative day (POD) 1 [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the psychological support dimension on postoperative day (POD) 1 [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the intraoperative remifentanil use [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the incidence of postoperative nausea and vomiting [<a href="#B26-nutrients-16-02375" class="html-bibr">26</a>,<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the severity of pain immediately after surgery (i.e., post-anesthesia care unit) [<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B31-nutrients-16-02375" class="html-bibr">31</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>] or at 24 h postoperatively [<a href="#B28-nutrients-16-02375" class="html-bibr">28</a>,<a href="#B32-nutrients-16-02375" class="html-bibr">32</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. CI: confidence interval. IV: invariance, Std: standardized, CI: confidence interval.</p>
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<p>Forest plot showing the impact of magnesium sulfate (MgSO4) on the extubation time [<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>] and length of post-anesthesia care unit (PACU) stay [<a href="#B27-nutrients-16-02375" class="html-bibr">27</a>,<a href="#B33-nutrients-16-02375" class="html-bibr">33</a>,<a href="#B34-nutrients-16-02375" class="html-bibr">34</a>]. CI: confidence interval. IV: invariance.</p>
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14 pages, 3138 KiB  
Systematic Review
Bovine Milk Fat Globule Membrane Supplementation and Neurocognitive Development: A Systematic Review and Meta-Analysis
by Therdpong Thongseiratch, Kulnipa Kittisakmontri and Nutthaporn Chandeying
Nutrients 2024, 16(14), 2374; https://doi.org/10.3390/nu16142374 (registering DOI) - 22 Jul 2024
Abstract
Given the limited evidence, there is no conclusive proof of the neurocognitive benefits of bovine milk fat globule membrane supplementation in infant formula. This study evaluates the neurocognitive benefits of bovine milk fat globule membrane supplementation in formula, comparing it to standard formula [...] Read more.
Given the limited evidence, there is no conclusive proof of the neurocognitive benefits of bovine milk fat globule membrane supplementation in infant formula. This study evaluates the neurocognitive benefits of bovine milk fat globule membrane supplementation in formula, comparing it to standard formula and assessing its noninferiority to breast milk. Data were sourced from studies published between January 2000 and March 2024 from PubMed, Cochrane Library, Web of Science, and Embase. Eight randomized controlled trials involving 1352 healthy term neonates, infants, and children up to 2 years old were included. Bovine milk fat globule membrane supplementation was significantly associated with improved cognitive development (mean difference: 3.29, 95% CI: 1.65 to 4.93, p < 0.001) and demonstrated minimal heterogeneity (I2 = 0%, p = 0.564). It showed significant improvement in executive function but not in language, motor, or social-emotional development. In non-inferiority analysis, there was no significant difference compared to breast milk regarding cognitive development. These findings support bovine milk fat globule membrane as a valuable addition to infant formula for cognitive benefits. Full article
(This article belongs to the Special Issue Focus on Diet and Nutrition in Early Life of Infants)
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<p>PRISMA 2020 flow diagram.</p>
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<p>Forest plot of association between MFGM supplementation and cognitive development; (<b>A</b>) shows effect size in difference in mean and (<b>B</b>) shows effect size in standard mean difference; MFGM, milk fat globule membrane; SF, standard formula [<a href="#B21-nutrients-16-02374" class="html-bibr">21</a>,<a href="#B22-nutrients-16-02374" class="html-bibr">22</a>,<a href="#B23-nutrients-16-02374" class="html-bibr">23</a>,<a href="#B27-nutrients-16-02374" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02374" class="html-bibr">28</a>].</p>
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<p>Forest plot of the association between MFGM supplementation and (<b>A</b>) language (including data from Nieto-Ruiz et al. 2020 [<a href="#B25-nutrients-16-02374" class="html-bibr">25</a>]), (<b>B</b>) motor, (<b>C</b>) social–emotional, and (<b>D</b>) executive function development (including data from Nieto-Ruiz et al. 2020 [<a href="#B26-nutrients-16-02374" class="html-bibr">26</a>]); MFGM, milk fat globule membrane; SF, standard formula [<a href="#B21-nutrients-16-02374" class="html-bibr">21</a>,<a href="#B22-nutrients-16-02374" class="html-bibr">22</a>,<a href="#B23-nutrients-16-02374" class="html-bibr">23</a>,<a href="#B24-nutrients-16-02374" class="html-bibr">24</a>,<a href="#B25-nutrients-16-02374" class="html-bibr">25</a>,<a href="#B26-nutrients-16-02374" class="html-bibr">26</a>,<a href="#B27-nutrients-16-02374" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02374" class="html-bibr">28</a>].</p>
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<p>Forest plot of association between MFGM-supplemented infant formula vs. breast milk and cognitive development; MFGM, milk fat globule membrane [<a href="#B21-nutrients-16-02374" class="html-bibr">21</a>,<a href="#B23-nutrients-16-02374" class="html-bibr">23</a>,<a href="#B27-nutrients-16-02374" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02374" class="html-bibr">28</a>].</p>
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<p>Funnel plots of studies assessing (<b>A</b>) cognitive, (<b>B</b>) language, (<b>C</b>) motor, and (<b>D</b>) social–emotional development.</p>
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<p>Risk-of-bias plot of each study [<a href="#B21-nutrients-16-02374" class="html-bibr">21</a>,<a href="#B22-nutrients-16-02374" class="html-bibr">22</a>,<a href="#B23-nutrients-16-02374" class="html-bibr">23</a>,<a href="#B24-nutrients-16-02374" class="html-bibr">24</a>,<a href="#B25-nutrients-16-02374" class="html-bibr">25</a>,<a href="#B26-nutrients-16-02374" class="html-bibr">26</a>,<a href="#B27-nutrients-16-02374" class="html-bibr">27</a>,<a href="#B28-nutrients-16-02374" class="html-bibr">28</a>].</p>
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13 pages, 1533 KiB  
Article
Association between Whole-Grain Intake and Obesity Defined by Different Anthropometric Indicators and Dose–Response Relationship Analysis among U.S. Adults: A Population-Based Study
by Yongjun Wang, Jing Feng, Tingting Liu, Zhaolong Gong and Qin Zhuo
Nutrients 2024, 16(14), 2373; https://doi.org/10.3390/nu16142373 (registering DOI) - 22 Jul 2024
Abstract
Existing research shows an inconsistent correlation between whole-grain intake and obesity risk, with limited study on the dose–response relationship. Here, we aimed to examine this association and dose–response relationship among U.S. adults who participated in a NHANES (2003–2018). The intake of whole grain [...] Read more.
Existing research shows an inconsistent correlation between whole-grain intake and obesity risk, with limited study on the dose–response relationship. Here, we aimed to examine this association and dose–response relationship among U.S. adults who participated in a NHANES (2003–2018). The intake of whole grain was collected and calculated from two rounds of 24 h dietary recall. Obesity was categorized based on body mass index (BMI) and waist circumference (WC). Weighted multivariable logistic regression models were used to calculate the odds of obesity according to whole-grain intake, and the dose–response relationship was modeled by restricted cubic spline regression. Among the 27,862 participants, 38.3% had general obesity, while 58.3% had abdominal obesity. After multivariate adjustment of potential confounders, the participants in the highest quintile of whole-grain intake had a lower prevalence of general obesity (OR 0.79; 95% CI 0.72–0.88) and abdominal obesity (OR 0.80; 95% CI 0.73–0.89) compared with those in the lowest category. Spline regression showed an inversely linear dose–response association between whole-grain intake and the prevalence of general obesity and abdominal obesity. In conclusion, a higher whole-grain intake was associated with lower odds of obesity, both general and abdominal. Our findings highlight the importance of increasing the whole-grain intake to prevent and manage obesity. Full article
(This article belongs to the Section Nutrition and Obesity)
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<p>Multivariable adjusted, dose–response associations between whole-grain intake and obesity for adults who participated in the NHANES (2003–2018). Association between whole -grain intake and obesity defined by body mass index for (<b>A</b>) all participants, (<b>B</b>) male participants, (<b>C</b>) female participants. Associations between whole-grain intake and obesity defined by waist circumference for (<b>D</b>) all participants, (<b>E</b>) male participants, (<b>F</b>) female participants. A restricted cubic spline regression model with three knots (5th, 50th, and 95th percentiles) was employed to estimate the dose–response associations between whole-grain intake and obesity. Odds ratios were adjusted for age, sex, race, education level, marital status, PIR, smoking status, drinking status, physical activity, sedentary time, energy intake, vegetable intake, fruit intake, meat intake, dairy intake, and added sugar intake. Light red shaded areas represent the 95% CI of odds ratios. <span class="html-italic">p</span> &gt; 0.05 for non-linearity in all cases.</p>
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<p>Multivariable adjusted, dose–response associations between whole-grain intake percentage of total grain intake and obesity for adults who participated in the NHANES (2003–2018). Association between whole-grain intake percentage and obesity defined by body mass index for (<b>A</b>) all participants, (<b>B</b>) male participants, (<b>C</b>) female participants. Associations between whole-grain intake percentage and obesity defined by waist circumference among (<b>D</b>) all participants, (<b>E</b>) male participants, (<b>F</b>) female participants. A restricted cubic spline regression model with three knots (5th, 50th, and 95th percentiles) was employed to estimate the dose–response associations between whole-grain intake percentage and obesity. Odds ratios were adjusted for age, sex, race, education level, marital status, PIR, smoking status, drinking status, physical activity, sedentary time, energy intake, vegetable intake, fruit intake, meat intake, dairy intake, and added sugar intake. Light red shaded areas represent the 95% CI of odds ratios. <span class="html-italic">p</span> &lt; 0.01 for non-linearity for (<b>A</b>) and (<b>C</b>), <span class="html-italic">p</span> &gt; 0.05 for non-linearity in the other cases.</p>
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<p>Flowchart of the study population in the NHANES from 2003 to 2018.</p>
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24 pages, 1189 KiB  
Review
Role of Gut Microbial Metabolites in the Pathogenesis of Primary Liver Cancers
by Maria Pallozzi, Valeria De Gaetano, Natalia Di Tommaso, Lucia Cerrito, Francesco Santopaolo, Leonardo Stella, Antonio Gasbarrini and Francesca Romana Ponziani
Nutrients 2024, 16(14), 2372; https://doi.org/10.3390/nu16142372 (registering DOI) - 22 Jul 2024
Abstract
Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver [...] Read more.
Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver necrosis and nodular regeneration. In this context, the gut–liver axis and gut microbiota have demonstrated a critical role in the pathogenesis of HCC, as dysbiosis and altered intestinal permeability promote bacterial translocation, leading to chronic liver inflammation and tumorigenesis through several pathways. A few data exist on the role of the gut microbiota or bacteria resident in the biliary tract in the pathogenesis of CCA, and some microbial metabolites, such as choline and bile acids, seem to show an association. In this review, we analyze the impact of the gut microbiota and its metabolites on HCC and CCA development and the role of gut dysbiosis as a biomarker of hepatobiliary cancer risk and of response during anti-tumor therapy. We also discuss the future application of gut microbiota in hepatobiliary cancer management. Full article
(This article belongs to the Special Issue Diet, Gut Microbiota, and Gastrointestinal Disease)
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<p>Gut dysbiosis and chronic inflammation leads to increased intestinal permeability, enhancing translocation of enterotoxins, bacteria and their fragments into the bloodstream. LPS and LTA share similar mechanisms, such as stimulating the TLR-MyD88-NFkB pathway, which is a well-known driver of inflammation and cell proliferation, and the activation of the COX2-PGE2 pathway, which causes DNA damage through the production of ROS. LPS also inhibits apoptosis in hepatocytes, enhancing cell replication and favoring the epithelial-to-mesenchymal cell transition. LTA also influences the phenotype of HSCs, leading to their senescence. BT also stimulates the upregulation of immune checkpoint molecules, resulting in increased levels of peripheral anergic cells, such as Tregs, and the loss of CD-8 T cells and NK cells. Abbreviations: LPS, lipopolysaccharide; LTA, lipoteichoic acid; TLR, Toll-like receptor; NFkB, nuclear factor k beta; COX2-PGE2, cyclooxygenase prostaglandin 2; JNK, Janus Kinase; IL, interleukin; SASP, senescence-associated secretory phenotype; HSCs, hepatic stellate cells; TIGIT, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif; PD1, Programmed Death 1; PD-L1, Programmed Death Ligand 1; CTLA-4, Cytotoxic T-Lymphocyte Antigen 4; ETM, epithelial-to-mesenchymal transition; ROS, reactive oxygen species; Tregs, regulatory T-cells; CD, cluster of differentiation; NK, natural killer.</p>
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<p>Gut dysbiosis leads to increased intestinal permeability and alterations of the gut–liver axis, leading to liver inflammation. The reiteration of this mechanism promotes an immunosuppressive microenvironment that favors the occurrence of primary liver cancers, including HCC and CCA. Moreover, during dysbiosis, a shift in gut-derived metabolites occurs, deeply influencing tumorigenesis. Dysbiosis is associated with BA retention and increased levels of secondary BAs, especially deoxycholic acid, which drives liver damage, aberrant liver cell proliferation and HCC promotion by the downregulation of FXR expression and the upregulation of the Wnt/β-catenin pathway. In CCA, a decrease in secondary BAs and changes in the glycoconjugated to tauroconjugated BAs ratio is described. High TMAO levels deriving from bacterial choline metabolism are associated with liver cancers, whereas high-choline diets exert a protective effect. Indole derivatives are important for immune cell development and intestinal barrier protection; a reduction in indole levels is typical of chronic liver diseases and high-fat diets. Among SCFAs, butyrate seems to have contradictory effects on HCC, sustaining cancer progression in some studies, and increasing immunotherapy efficacy in others, whereas butyrate seems to reduce cell mitosis in CCA. COnversely, acetate can contrast HCC progression by ILC3 inhibition and interfering with HDAC activity. Ethanol is a well-recognized carcinogenic agent; other than diet, increased ethanol plasma levels can derive from ethanol-producing bacteria, such as <span class="html-italic">Klebsiella pneumoniae</span>, which is over-represented in gut dysbiosis. Finally, high BCAA tumor levels and high BCAA intratumor metabolism have been associated with HCC and CCA. Differently, BCAA administration with diet seems to inhibit this process, suggesting a reciprocal relationship between dysbiosis and BCAA metabolism. Abbreviations: HCC: hepatocellular carcinoma; CCA: cholangiocarcinoma; FXR: farnesoid X receptor; TMAO: trimethylamine N-oxide; SCFAs: short-chain fatty acids; HDACs: histone deacetylases; BCAAs: branched-chain amino acids; ILC3s: type 3 innate lymphoid cells; BAs: bile acids. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a>.</p>
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13 pages, 647 KiB  
Article
Deficiency of Energy and Nutrient and Gender Differences among Chinese Adults: China Nutrition and Health Survey (2015–2017)
by Xiaoqi Wei, Liyun Zhao, Hongyun Fang, Mulei Chen, Wei Piao, Lahong Ju, Shuya Cai, Yuxiang Yang, Yuge Li, Fusheng Li, Jiaxi Li, Jing Nan and Dongmei Yu
Nutrients 2024, 16(14), 2371; https://doi.org/10.3390/nu16142371 (registering DOI) - 22 Jul 2024
Abstract
Half of Chinese adults face the double burden of overweight/obesity and micronutrient deficiencies, and nearly 40% of them are severely overweight/obese or have micronutrient deficiencies. This study used the data from China Nutrition and Health Survey (CNHS) from 2015 to 2017 to estimate [...] Read more.
Half of Chinese adults face the double burden of overweight/obesity and micronutrient deficiencies, and nearly 40% of them are severely overweight/obese or have micronutrient deficiencies. This study used the data from China Nutrition and Health Survey (CNHS) from 2015 to 2017 to estimate the prevalence of inadequate dietary micronutrient intake (including vitamin A, vitamin B1, vitamin B2, vitamin C, cCalcium, iron and sodium) in Chinese adults and further determine the differences in micronutrient intake by gender, age and BMI. A total of 61,768 subjects were included in this study, of which 33,262 (54%) were female. The intake of energy and all macronutrients decreased with age, and the intake was higher in men than in women. Inadequate energy intake occurs in adults of all ages. In terms of nutrient intake, women had a higher rate of insufficient carbohydrate intake than men in all age groups. Inadequate protein intake was more common in women aged 18–49 years (60.9%) than in men. Compared with women, men had a higher rate of vitamin B2 intake. Insufficient vitamin B3 intake was more common in women aged 18–49 years (35.6%), men aged 65–79 years (39.7%) and men aged 80 years and above (47.9%). In all age groups, insufficient vitamin C intake is higher in women than in men—up to 85.8 percent in women aged 80 years old and above. Compared with men in the same age group, insufficient intake of calcium and iron is more obvious in women. Women have significantly higher rates of inadequate intake of calcium, iron and sodium than men. In the analysis of correlations between BMI or demographic data and micronutrient intakes, the likelihood of micronutrient intakes being insufficient was higher in the central and western regions in all age groups compared to the eastern regions. The risk of insufficient micronutrient intake was higher in obese men and women aged 18–49 years and 50–64 years. Underweight and overweight women in the 65–79 age group were more likely to have inadequate micronutrient intake. Obese women over 80 years of age were less likely to have inadequate micronutrient intake. No significant difference was found between urban and rural areas for each age group. Full article
(This article belongs to the Special Issue Dietary Patterns, Dietary Intake, Dietary Behaviours and Health)
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<p>Proportions (%) of insufficient intake per age group and gender.</p>
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<p>Proportions (%) of excessive nutrients per age group and gender.</p>
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20 pages, 2921 KiB  
Article
Health-Promoting Potential of Mandarin Pomace Extracts Enriched with Phenolic Compounds
by Adriana Maite Fernández-Fernández, Eduardo Dellacassa, Romina Curbelo, Tiziana Nardin, Roberto Larcher, Alejandra Medrano-Fernandez and María Dolores del Castillo
Nutrients 2024, 16(14), 2370; https://doi.org/10.3390/nu16142370 (registering DOI) - 22 Jul 2024
Abstract
The aim of this work was to assess the effect of in vitro human digestion on the chemical composition (carbohydrates and phenolic compounds) and bioactivity of hydro-alcoholic-acid pomace extracts from two mandarin varieties (Clemenule and Ortanique) by measuring their antioxidant, antidiabetic, anti-glycative, hypolipidemic, [...] Read more.
The aim of this work was to assess the effect of in vitro human digestion on the chemical composition (carbohydrates and phenolic compounds) and bioactivity of hydro-alcoholic-acid pomace extracts from two mandarin varieties (Clemenule and Ortanique) by measuring their antioxidant, antidiabetic, anti-glycative, hypolipidemic, and anti-inflammatory properties. The phenolic compound profile showed that nobiletin was the main flavonoid found in the extracts and digests of Clemenule pomace and extract, while isosinensetin/sinensetin/tangeretin were the ones in the Ortanique samples. The digests of Clemenule and Ortanique extracts showed Folin reaction values of 9.74 and 9.20 mg gallic acid equivalents (GAE)/g of sample, ABTS values of 83.2 and 91.7 µmol Trolox equivalents (TE)/g of sample, and ORAC-FL values of 142.8 and 891.6 µmol TE/g of sample, respectively. Extracts (50–500 µg/mL) inhibited intracellular reactive oxygen species (ROS) formation in CCD-18Co cells under physiological and oxidative-induced conditions. Clemenule and Ortanique extract digests showed IC50 values of 13.50 and 11.07 mg/mL for α-glucosidase, 28.79 and 69.64 mg/mL for α-amylase, and 16.50 and 12.77 mg/mL for AGEs, and 2.259 ± 0.267 and 0.713 ± 0.065 mg/mL for pancreatic lipase inhibition, respectively. Ortanique extract (250–1000 µg/mL) inhibited the production of nitric oxide in RAW264.7 macrophages under inflammation-induced conditions, and intracellular ROS formation. In conclusion, altogether, the results supported the potential of mandarin extracts to be used as health promoters by reducing the risk of non-communicable chronic diseases. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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<p>Scheme of the research carried out in the current work.</p>
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<p>ROS production on CCD-18Co colon cells by undigested Ortanique and Clemenule extracts (<b>a</b>–<b>c</b>). Physiological ROS: 24 h incubation of cells with the samples (<b>a</b>). Pre-treatment ROS: 24 h incubation of cells with the samples, then 30 min incubation with only t-BOOH (<b>b</b>). Pre-treatment with co-ad ROS: 24 h incubation of cells with the samples, then 30 min incubation with samples and t-BOOH (<b>c</b>). Ascorbic acid (Asc, 10 µg/mL) was tested as an antioxidant of reference. Bars represent the mean values and error bars represent the standard error. Lowercase letters indicate significant differences between the samples that present them (LSD Fisher, <span class="html-italic">p</span> &lt; 0.05). Capital letters indicate significant differences between the samples that present them (LSD Fisher, <span class="html-italic">p</span> &lt; 0.05). All determinations were performed in triplicate in three different cell passages.</p>
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<p>Pancreatic lipase inhibition capacity of mandarin pomaces and their respective extracts, as well as standards of phenolic compounds.</p>
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<p>Effects of Ortanique extract, glucosamine, and positive (C+) and negative (C−) controls on LPS-induced (1 µg/mL) NO oxide production in RAW264.7 cells in the pre-treatment (<b>a</b>) and pre-treatment with co-administration (<b>b</b>) assays. Glucosamin was used as an anti-inflammatory agent of reference. They were incubated with samples for 24 h, and afterwards, samples were taken out in order to add LPS 1 µg/mL (pre-treatment) or sample with LPS 1 µg/mL (pre-treatment with co-administration) for 24 h. Supernatants were transferred to a new 96-well plate to react with Griess reagent through a 15 min incubation (room temperature in the dark) and absorbance was measured at 550 nm. NO standard curve was measured in parallel. Bars represent the mean values in NO concentration and error bars represent the standard deviation. Statistical analysis was carried out between the values in the same assay, indicating significant differences by different letters (Tukey test, <span class="html-italic">p</span> &lt; 0.05). Results were compiled from triplicate measurements from three different cell passages.</p>
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<p>ROS production inhibition by Ortanique and Clemenule extracts tested in RAW264.7 macrophages. Physiological (<b>a</b>) and induced (<b>b</b>) % ROS were determined by 24 h incubation with samples (physiological (<b>a</b>)), followed by 30 minutes of incubation with samples and t-BOOH (pre-treatment with co-administration (<b>b</b>)). Bars and error bars represent the mean values and standard errors, respectively. Lowercase letters indicate significant differences between the samples that present them (LSD Fisher, <span class="html-italic">p</span> &lt; 0.05). Capital letters indicate significant differences between the samples that present them (LSD Fisher, <span class="html-italic">p</span> &lt; 0.05). Results were compiled from triplicate measurements from three different cell passages.</p>
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<p>Mechanisms of action of the phenolic compounds of mandarin pomace extracts to counteract type 2 diabetes and obesity.</p>
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13 pages, 1474 KiB  
Article
Manuka Honey Inhibits Human Breast Cancer Progression in Preclinical Models
by Diana C. Márquez-Garbán, Cristian D. Yanes, Gabriela Llarena, David Elashoff, Nalo Hamilton, Mary Hardy, Madhuri Wadehra, Susan A. McCloskey and Richard J. Pietras
Nutrients 2024, 16(14), 2369; https://doi.org/10.3390/nu16142369 (registering DOI) - 22 Jul 2024
Abstract
Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast [...] Read more.
Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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<p>Manuka honey reduces the proliferation of ER-positive human breast cancer cells in vitro. ER-positive MCF-7 breast cancer cells and TNBC MDA-MB-231 cells were incubated in the presence of increasing concentrations of either (<b>A</b>) Manuka honey at 0.0 to 5.0% (<span class="html-italic">w</span>/<span class="html-italic">v</span>) or (<b>B</b>) Manuka powder at 0.0–16%. After 72 h, cell counts were performed using an MTS assay and by manual cell counts. The figures show tumor cell proliferation expressed as the mean percentage of vehicle-treated controls with SEM. Experiments were performed at least three times in independent experiments. (<b>C</b>) Manuka honey reduces the proliferation of MCF-7 cancer cells but not that of non-malignant mammary cells in vitro and enhances the antitumor action of the antiestrogen tamoxifen. Human MCF-7 tumor cells and non-malignant HMECs were cultured in vitro with 2.5% <span class="html-italic">w/v</span> Manuka honey (MH), 10 μM tamoxifen (TM), or both agents combined for 48 h. Cell proliferation was then quantitated and expressed as a percentage of that recorded in appropriate vehicle-treated controls. A higher 5% <span class="html-italic">w/v</span> MH concentration was also tested without a significant effect on HMEC proliferation. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.01, n &gt; 3.</p>
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<p>Induction of apoptosis of breast cancer cells by Manuka honey. (<b>A</b>) MCF-7 cells were treated with vehicle control (CON), 2.5% (<span class="html-italic">w</span>/<span class="html-italic">v</span>) (MH 2.5) or 5% (<span class="html-italic">w</span>/<span class="html-italic">v</span>) (MH 5.0) Manuka honey, camptothecin 1 μM (Cam), 5% (<span class="html-italic">w</span>/<span class="html-italic">v</span>) (Dex) dextrose, or 5% (<span class="html-italic">w</span>/<span class="html-italic">v</span>) (HMesq) Mesquite honey. After 24 and/or 48 h, cells were harvested and stained with Annexin V and 7-AAD to assess early and late apoptosis. Treatments with Manuka honey, particularly at 5.0% (<span class="html-italic">w</span>/<span class="html-italic">v</span>), elicited significant increments in apoptotic cells as compared to controls (* <span class="html-italic">p</span> &lt; 0.05). Camptothecin, a positive control drug, elicited a similar increase in late apoptotic cells after 48 h, while treatment of MCF-7 cells with dextrose or Mesquite honey did not exhibit comparable increments in the numbers of apoptotic cells. (<b>B</b>) Treatment of MCF-7 cells with Manuka honey elicits increased poly (ADP-ribose) polymerase (PARP) cleavage. Cells were treated in vitro for 48 h with either control vehicle or Manuka honey at 0.6, 2.5, or 5.0% (<span class="html-italic">w</span>/<span class="html-italic">v</span>). Camptothecin was also used as a positive control.</p>
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<p>Manuka honey activates AMPK signaling and inhibits mTOR and STAT3 downstream signaling. (<b>A</b>) MCF7 cells were treated with increasing concentrations of Manuka honey (0–5%) and 5% Mesquite honey as control. After 24 h, cells were lysed and immunoblotted with specific antibodies. (<b>B</b>) MCF7 cells were treated with increasing concentrations of Manuka honey 0.3–5% (<span class="html-italic">w</span>/<span class="html-italic">v</span>). After 24 h, cells were lysed, and whole cell extracts were resolved by PAGE and immunoblotted with specific antibodies.</p>
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<p>Antitumor activity of Manuka honey in human breast cancer xenografts in vivo. Ovariectomized nude mice (nu<sup>−</sup>/nu<sup>−</sup>, Charles Rivers) with estradiol supplements were implanted with MCF-7 tumor xenografts SQ and treated with Manuka honey or control administered by oral gavage after tumors achieved a size of 50–75 cm<sup>3</sup>. Oral gavage (0.1 mL volume) with 50% (<span class="html-italic">w</span>/<span class="html-italic">v</span>) Manuka honey or control was performed twice daily from days 1 to 14, then once daily thereafter to day 42. Treatment with Manuka honey administered orally elicited a significant suppression of MCF-7 xenograft progression as compared to controls (** <span class="html-italic">p</span> &lt; 0.01) n = 5–7 mice per group.</p>
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12 pages, 1235 KiB  
Article
Modulation of the Serum Metabolome by the Short-Chain Fatty Acid Propionate: Potential Implications for Its Cholesterol-Lowering Effect
by Johann Roessler, Friederike Zimmermann, Paul Schumann, Vanasa Nageswaran, Pegah Ramezani Rad, Sven Schuchardt, David M. Leistner, Ulf Landmesser and Arash Haghikia
Nutrients 2024, 16(14), 2368; https://doi.org/10.3390/nu16142368 (registering DOI) - 22 Jul 2024
Abstract
(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism. [...] Read more.
(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism. Here, we investigated the effects of oral PA supplementation on the human serum metabolome and analyzed changes in the serum metabolome in relation to the cholesterol-lowering properties of PA. (2) Methods: The serum metabolome of patients supplemented with either placebo or propionate orally for 8 weeks was assessed using a combination of flow injection analysis-tandem (FIA-MS/MS) as well as liquid chromatography (LC-MS/MS) and mass spectrometry using a targeted metabolomics kit (MxP®Quant 500 kit: BIOCRATES Life Sciences AG, Innsbruck, Austria). A total of 431 metabolites were employed for further investigation in this study. (3) Results: We observed a significant increase in distinct bile acids (GCDCA: fold change = 1.41, DCA: fold change = 1.39, GUDCA: fold change = 1.51) following PA supplementation over the study period, with the secondary bile acid DCA displaying a significant negative correlation with the serum cholesterol levels. (4) Conclusions: Oral supplementation with PA modulates the serum metabolome with a particular impact on the circulatory bile acid profile. Since cholesterol and bile acid metabolism are interconnected, the elevation of the secondary bile acid DCA may contribute to the cholesterol-lowering effect of PA. Full article
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<p>Placebo-Metabolomics T2 vs. T1. Data are presented on the <span class="html-italic">x</span>-axis as fold change, calculated as the ratio between serum concentration (µmol/L) at T2 divided by serum concentration at T1. Data are further outlined with the individual <span class="html-italic">p</span>-value in the <span class="html-italic">y</span>-axis, determined by comparison of means of serum concentration between the two timepoints using paired Student’s <span class="html-italic">t</span>-test or Wilcoxon test where eligible. Grey dots indicate not significantly altered metabolites.</p>
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<p>PA-Metabolomics T2 vs. T1. Data are presented in the <span class="html-italic">x</span>-axis as fold change, calculated as the ratio between serum concentration (µmol/L) at T2 divided by serum concentration at T1. Individual <span class="html-italic">p</span>-values are provided on the <span class="html-italic">y</span>-axis, determined by a comparison of means of serum concentration between the two timepoints using paired Student’s <span class="html-italic">t</span>-test or Wilcoxon test where eligible. Grey dots indicate not significantly altered metabolites. Key: GUDCA—Glycoursodeoxycholic acid; DCA—deoxycholic acid; GCDCA—Glycochenodeoxycholic acid.</p>
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<p>Correlation analysis between bile acids and cholesterol levels upon PA treatment. (<b>A</b>) Data are presented as Pearson/Spearman’s r in the correlation coefficient matrix. +1.0 indicates a positive correlation, −1.0 indicates a negative correlation. (<b>B</b>) Pearson/Spearman’s correlation—<span class="html-italic">p</span>-values. Bold values display significant <span class="html-italic">p</span>-values. Key: GUDCA—Glycoursodeoxycholic acid; DCA—deoxycholic acid; GCDCA—Glycochenodeoxycholic acid; TC—total cholesterol; LDL-C—low-density lipoprotein-cholesterol; HDL-C—high-density lipoprotein-cholesterol.</p>
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12 pages, 594 KiB  
Article
Association of Dietary Selenium Intake with Type 2 Diabetes in Middle-Aged and Older Adults in China
by Fangyuan Li, Xi Hong, Huijun Wang, Weiyi Li, Lili Chen, Liusen Wang, Boya Zhao, Shaoshunzi Wang, Hongru Jiang and Zhihong Wang
Nutrients 2024, 16(14), 2367; https://doi.org/10.3390/nu16142367 (registering DOI) - 21 Jul 2024
Abstract
The relationship between distinct dietary selenium intake and type 2 diabetes (T2D) is still a topic of uncertainty. This study examined the relationship between dietary selenium intake and T2D risk among middle-aged and older Chinese adults. Dietary selenium intake was assessed through three [...] Read more.
The relationship between distinct dietary selenium intake and type 2 diabetes (T2D) is still a topic of uncertainty. This study examined the relationship between dietary selenium intake and T2D risk among middle-aged and older Chinese adults. Dietary selenium intake was assessed through three 24 h recalls, using data from the China Health and Nutrition Survey. To investigate the relationship and the potential dose–response pattern between selenium intake and the likelihood of developing T2D, we employed both the restricted cubic spline analysis and the Cox proportional hazards model as our analytical tools. A cohort of 5970 participants aged ≥ 50 years was followed for an average of 5.44 years. The results revealed a V-shaped correlation between selenium intake and T2D risk, with the lowest risk observed at approximately 45 µg/day. Below this level, the risk decreased with an increasing selenium intake, while the risk increased between 45 and 100 µg/day. No significant association was found beyond 100 µg/day. These findings suggest that both low and high selenium consumption may increase T2D risk, highlighting the importance of maintaining a balanced selenium intake for T2D prevention. Full article
(This article belongs to the Section Geriatric Nutrition)
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<p>Flowchart of subjects.</p>
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<p>Dose–response relationship between dietary selenium intake and risk of T2D. Restricted cubic spline of association between dietary selenium intake and Type 2 diabetes. The red-shaded area represents the 95% confidence interval (CI).</p>
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20 pages, 1731 KiB  
Review
Correlation between Alzheimer’s Disease and Gastrointestinal Tract Disorders
by Julia Kuźniar, Patrycja Kozubek, Magdalena Czaja and Jerzy Leszek
Nutrients 2024, 16(14), 2366; https://doi.org/10.3390/nu16142366 (registering DOI) - 21 Jul 2024
Abstract
Alzheimer’s disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-β in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of [...] Read more.
Alzheimer’s disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-β in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer’s disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota–gut–brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options. Full article
(This article belongs to the Special Issue Nutrition, Gut Microbiome and Metabolism)
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<p>Flow diagram for the identification of selected studies.</p>
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<p>Pathogenetic factors of <span class="html-italic">H. pylori</span> in Alzheimer’s disease onset.</p>
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<p>Microbiota–gut–brain axis.</p>
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<p>Role of gut dysbiosis in Alzheimer’s disease [<a href="#B29-nutrients-16-02366" class="html-bibr">29</a>].</p>
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<p>Neurotransmitters, synapses and cytokines in Alzheimer’s disease progression.</p>
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15 pages, 1624 KiB  
Article
Dietary Knowledge, Attitude, Practice Survey and Nutritional Knowledge-Based Intervention: A Cross-Sectional and Randomized Controlled Trial Study among College Undergraduates in China
by Junjie Wu, Wei Yu, Zhuo Xu, Yuxuan Chen, Jiaomei Li and Qinghua Sun
Nutrients 2024, 16(14), 2365; https://doi.org/10.3390/nu16142365 (registering DOI) - 21 Jul 2024
Abstract
Background: Understanding undergraduates’ dietary literacy, including dietary knowledge, attitude and practice (KAP), is important for future health promotion policies. Therefore, this study aimed to investigate the current status and influencing factors of dietary literacy in Chinese college undergraduates and explore whether a nutritional [...] Read more.
Background: Understanding undergraduates’ dietary literacy, including dietary knowledge, attitude and practice (KAP), is important for future health promotion policies. Therefore, this study aimed to investigate the current status and influencing factors of dietary literacy in Chinese college undergraduates and explore whether a nutritional lecture could improve their dietary literacy. Methods: This study included two parts: a cross-sectional study (n = 1026) conducted by a dietary literacy questionnaire, and a randomized controlled trail (RCT) that enrolled 99 college undergraduates who were randomized to a control group or a nutritional lecture group. Data from the questionnaire and 72 h food records were obtained on day 0, day 3 and day 100 before and after intervention. Results: This cross-sectional study showed that the mean scores of dietary KAP were respectively 100.0 (33.3), 59.1 (13.6) and 71.7 (11.7), with an excellent rate of 36.6%, 1.9% and 3.4%. Female upper-grade undergraduates and those with medicine-related majors illustrated higher dietary knowledge scores (p < 0.001). Dietary attitude rather than dietary knowledge had a significant impact on dietary practice (p < 0.001). This finding was in line with the results in the RCT study. Compared with the control group, dietary knowledge was significantly improved in the nutritional lecture group on both day 3 (p = 0.002) and day 100 (p = 0.023) after intervention. However, dietary behavior was improved only on day 3 post nutritional lecture (p = 0.029) but decreased to the original level 100 days later (p < 0.001). Conclusions: This study discovered the unsatisfying status and discrepancy between dietary literacy among college undergraduates of different sex, majors and college years. Dietary attitude instead of dietary knowledge was discovered as a determining role in dietary practice. One nutritional lecture could improve undergraduates’ dietary literacy but the effect was not long-lasting. Further studies with more reinforced and durable interventions are warranted. Full article
(This article belongs to the Section Nutritional Policies and Education for Health Promotion)
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<p>Study design. Notes: KAP (knowledge, attitude, practice); ZCMU (Zhejiang Chinese Medical University).</p>
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<p>Distribution of dietary KAP literacy scores among college students. (<b>a</b>) Boxplots of questionnaire respondents’ dietary knowledge, attitude and practice scores. (<b>b</b>) Percentage bar graphs of undergraduates with different levels of dietary KAP.</p>
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<p>Comparisons of dietary knowledge scores of undergraduates among different sex, college years and majors. (<b>a</b>) Sex and dietary knowledge scores: female undergraduates achieved higher dietary knowledge scores than male students. (<b>b</b>) College year and dietary knowledge scores: upper-grade undergraduates achieved higher dietary knowledge scores than lower-grade students. (<b>c</b>) Major and dietary knowledge scores: medicine-related undergraduates achieved higher dietary knowledge scores than students majoring in literature and art and science and engineering. (<b>d</b>) Different medicine-related major and dietary knowledge scores: undergraduates majoring in nursing and traditional Chinese medicine achieved higher dietary knowledge grades than students majoring in preventive medicine and medical technology and information engineering. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Scatter plot of the association among dietary KAP scores. (<b>a</b>) Insignificant association between dietary knowledge and dietary attitude. (<b>b</b>) Insignificant association between dietary knowledge and dietary practice. (<b>c</b>) Significant association between dietary attitude and dietary practice.</p>
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<p>Impact of nutritional lecture on dietary literacy. (<b>a</b>) Significant difference in dietary knowledge scores shown on day 3 and day 100 after intervention and insignificant difference shown on day 0 between the two groups. (<b>b</b>) Significant difference in dietary attitude scores shown on day 100 and insignificant difference on day 0 and day 3 between the two groups. (<b>c</b>) Insignificant difference in the dietary practice scores between the two groups shown on days 0, 3 and 100. (<b>d</b>) Trends of dietary quality of the two groups. The nutritional lecture group showed a significant improvement in dietary quality scores on day 3 and a significant decrease on day 100. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, ns (not significant).</p>
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14 pages, 2051 KiB  
Article
S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation
by Yu-Chen Hu, Tzu-Ching Huang, Li-Wen Huang, Hsiao-Ling Cheng, Bau-Shan Hsieh and Kee-Lung Chang
Nutrients 2024, 16(14), 2364; https://doi.org/10.3390/nu16142364 (registering DOI) - 21 Jul 2024
Abstract
Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. [...] Read more.
Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague–Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation. Full article
(This article belongs to the Special Issue The Role of Nutrition in Osteoarthritis Development)
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<p>Serum levels of cholesterol and triglycerides in the control sham and OVX-OA rats without or with S-equol supplementation. The details of the OVX-OA rat groups are described in <a href="#sec2dot2-nutrients-16-02364" class="html-sec">Section 2.2</a>. After S-equol supplementation for 8 weeks, levels of (<b>A</b>) cholesterol and (<b>B</b>) triglycerides in serum were analyzed by enzymatic kits. The results are presented as means ± S.D. (<span class="html-italic">n</span> = 9). Groups with different letters show a significant difference, while those with the same letter show no significant difference. A <span class="html-italic">p</span>-value &lt; 0.05 was considered statistically significant.</p>
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<p>Articular cartilage morphology and histology in the control sham and OVX-OA rats without or with S-equol supplementation. The details of the OVX-OA rat groups are described in <a href="#sec2dot2-nutrients-16-02364" class="html-sec">Section 2.2</a>. (<b>A</b>) Images of the articular surfaces of the femoral groove. (<b>B</b>) Joint cartilage histomorphological changes stained with Safranin O/Fast green. Red indicates proteoglycan. Scale bar: 100 μm. (<b>C</b>) OARSI score of each joint. The results are presented as means ± S.D. (<span class="html-italic">n</span> = 9). Groups with different letters show a significant difference, while those with the same letter show no significant difference. A <span class="html-italic">p</span>-value &lt; 0.05 was considered statistically significant.</p>
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<p>Serum levels of bone turnover biomarkers of PINP, CTX-I, and NTX-I in the control sham and OVX-OA rats without or with S-equol supplementation. The details of the OVX-OA rat groups are described in <a href="#sec2dot2-nutrients-16-02364" class="html-sec">Section 2.2</a>. After S-equol supplementation for 8 weeks, levels of (<b>A</b>) PINP, (<b>B</b>) CTX-I, and (<b>C</b>) NTX-I in serum were analyzed by enzyme-linked immunosorbent assay. The results are presented as means ± S.D. (<span class="html-italic">n</span> = 9). Groups with different letters show a significant difference, while those with the same letter show no significant difference. A <span class="html-italic">p</span>-value &lt; 0.05 was considered statistically significant.</p>
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<p>Serum levels of HA and PIINP cartilage degradation biomarkers in the control sham and OVX-OA rats without or with S-equol supplementation. The details of the OVX-OA rat groups are described in <a href="#sec2dot2-nutrients-16-02364" class="html-sec">Section 2.2</a>. After S-equol supplementation for 8 weeks, levels of (<b>A</b>) HA and (<b>B</b>) PIINP in serum were analyzed by enzyme-linked immunosorbent assay. The results are presented as means ± S.D. (<span class="html-italic">n</span> = 9). Groups with different letters have a significant difference, while those with the same letter show no significant difference. A <span class="html-italic">p</span>-value &lt; 0.05 was considered statistically significant.</p>
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<p>Serum levels of MMP-1, MMP-3, and MMP-13 matrix-degrading enzymes in the control sham and OVX-OA rats without or with S-equol supplementation. The details of the OVX-OA rat groups are described in <a href="#sec2dot2-nutrients-16-02364" class="html-sec">Section 2.2</a>. After S-equol supplementation for 8 weeks, levels of (<b>A</b>) MMP-1, (<b>B</b>) MMP-3, and (<b>C</b>) MMP-13 in serum were analyzed by enzyme-linked immunosorbent assay. The results are presented as means ± S.D. (<span class="html-italic">n</span> = 9). Groups with different letters show a significant difference, while those with the same letter show no significant difference. A <span class="html-italic">p</span>-value &lt; 0.05 was considered statistically significant.</p>
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<p>Serum levels of H<sub>2</sub>O<sub>2</sub> and NO in the control sham and OVX-OA rats without or with S-equol supplementation. The details of the OVX-OA rat groups are described in <a href="#sec2dot2-nutrients-16-02364" class="html-sec">Section 2.2</a>. After S-equol supplementation for 8 weeks, levels of (<b>A</b>) H<sub>2</sub>O<sub>2</sub> and (<b>B</b>) NO were analyzed using a colorimetric assay kit. The results are presented as means ± S.D. (<span class="html-italic">n</span> = 9). Groups with different letters show a significant difference, while those with the same letter show no significant difference. A <span class="html-italic">p</span>-value &lt; 0.05 was considered statistically significant.</p>
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20 pages, 869 KiB  
Review
Neurodevelopment Is Dependent on Maternal Diet: Placenta and Brain Glucose Transporters GLUT1 and GLUT3
by Tomoko Daida, Bo-Chul Shin, Carlos Cepeda and Sherin U. Devaskar
Nutrients 2024, 16(14), 2363; https://doi.org/10.3390/nu16142363 (registering DOI) - 21 Jul 2024
Abstract
Glucose is the primary energy source for most mammalian cells and its transport is affected by a family of facilitative glucose transporters (GLUTs) encoded by the SLC2 gene. GLUT1 and GLUT3, highly expressed isoforms in the blood–brain barrier and neuronal membranes, respectively, are [...] Read more.
Glucose is the primary energy source for most mammalian cells and its transport is affected by a family of facilitative glucose transporters (GLUTs) encoded by the SLC2 gene. GLUT1 and GLUT3, highly expressed isoforms in the blood–brain barrier and neuronal membranes, respectively, are associated with multiple neurodevelopmental disorders including epilepsy, dyslexia, ADHD, and autism spectrum disorder (ASD). Dietary therapies, such as the ketogenic diet, are widely accepted treatments for patients with the GLUT1 deficiency syndrome, while ameliorating certain symptoms associated with GLUT3 deficiency in animal models. A ketogenic diet, high-fat diet, and calorie/energy restriction during prenatal and postnatal stages can also alter the placental and brain GLUTs expression with long-term consequences on neurobehavior. This review focuses primarily on the role of diet/energy perturbations upon GLUT isoform-mediated emergence of neurodevelopmental and neurodegenerative disorders. Full article
(This article belongs to the Special Issue Nutrition and Dietary Patterns: Effects on Brain Function)
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<p>The transport mechanisms underlying transfer of glucose, ketone body, and lactate across the blood–brain barrier from capillary vessels to neurons and astrocytes. GLUT; glucose transporter, MCT; monocarboxylate transporters.</p>
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18 pages, 1068 KiB  
Article
The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status
by Karolina Kowalcze, Robert Krysiak, Giuseppe Gullo and Johannes Ott
Nutrients 2024, 16(14), 2362; https://doi.org/10.3390/nu16142362 (registering DOI) - 21 Jul 2024
Abstract
Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic–pituitary–gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the [...] Read more.
Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic–pituitary–gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit. Full article
(This article belongs to the Special Issue Vitamins and Human Health: 2nd Edition)
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<p>The flow of the participants through the study.</p>
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<p>Average curves of reproductive hormones and organ sizes in infant girls during the first 18 months of life. Estradiol concentration, FSH concentration, LH concentration, ovarian volume, uterus length and breast diameter are expressed as normalized values (mean hormone concentration/mean organ size divided by their maximum value). Abbreviations: FSH—follicle-stimulating hormone; LH—luteinizing hormone.</p>
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9 pages, 747 KiB  
Article
Breakfast Frequency and Smoking Initiation in University Students: A Retrospective Cohort Study
by Rika Mori, Ryohei Yamamoto, Maki Shinzawa, Naoko Otsuki, Yuichiro Matsumura, Yuko Nakamura, Qinyan Li, Yusuke Sakaguchi, Isao Matsui, Masayuki Mizui, Haruki Shinomiya, Chisaki Ishibashi, Kaori Nakanishi, Daisuke Kanayama and Izumi Nagatomo
Nutrients 2024, 16(14), 2361; https://doi.org/10.3390/nu16142361 (registering DOI) - 21 Jul 2024
Abstract
Smoking causes various health problems. Limited studies have reported a clinical effect of skipping breakfast on smoking initiation among adolescents. This retrospective cohort study aimed to assess the dose-dependent association between skipping breakfast and smoking initiation in university students. This study included 17,493 [...] Read more.
Smoking causes various health problems. Limited studies have reported a clinical effect of skipping breakfast on smoking initiation among adolescents. This retrospective cohort study aimed to assess the dose-dependent association between skipping breakfast and smoking initiation in university students. This study included 17,493 male and 8880 female students aged 18−22 years at a national university in Japan. The association between breakfast frequency (eating every day and skipping occasionally, often, and usually) and smoking initiation was evaluated using Cox proportional hazards models adjusted for clinically relevant factors. Smoking initiation was observed in 2027 (11.6%) male and 197 (2.2%) female students over the median observational period of 3.0 and 3.1 years. Skipping breakfast was significantly associated with smoking initiation in a dose-dependent fashion in male students (the adjusted hazard ratios [95% confidence interval] of eating breakfast every day and skipping occasionally, often, and usually: 1.00 [reference], 1.30 [1.15, 1.46], 1.47 [1.21, 1.79], and 1.77 [1.40, 2.25], respectively). Female students skipping breakfast occasionally and often were more vulnerable to smoking initiation than those who ate breakfast every day (1.00 [reference], 1.86 [1.24, 2.78], 2.97 [1.66, 5.32], and 1.76 [0.55, 5.64], respectively). Breakfast frequency may be useful to identify university students at risk of smoking initiation who need improvement in their health literacy. Full article
(This article belongs to the Section Nutritional Policies and Education for Health Promotion)
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<p>Flowchart depicting inclusion and exclusion of study participants.</p>
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<p>Baseline breakfast frequency and smoking initiation in 17,493 male (<b>a</b>) and 8880 female (<b>b</b>) students.</p>
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23 pages, 3933 KiB  
Article
Digestive Profiles of Human Milk, Recombinant Human and Bovine Lactoferrin: Comparing the Retained Intact Protein and Peptide Release
by Bum Jin Kim, Russell F. Kuhfeld, Joanna L. Haas, Yanisa M. Anaya, Raysa Rosario Martinez, Baidya Nath P. Sah, Bella Breen, Kahler Newsham, Carrie-Anne Malinczak and David C. Dallas
Nutrients 2024, 16(14), 2360; https://doi.org/10.3390/nu16142360 (registering DOI) - 21 Jul 2024
Abstract
Lactoferrin (LF) is a major component of human milk. LF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults. No recombinant human lactoferrin (rhLF) is available for commercial food use. To determine the extent to which rhLF (Effera™) [...] Read more.
Lactoferrin (LF) is a major component of human milk. LF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults. No recombinant human lactoferrin (rhLF) is available for commercial food use. To determine the extent to which rhLF (Effera™) produced by Komagataella phaffii digests similarly to hmLF, a validated in vitro digestion protocol was carried out. Bovine LF (bLF) was used as an additional control, as it is approved for use in various food categories. This study compared the extent of intact protein retention and the profile of peptides released in hmLF, bLF and rhLF (each with low and high iron saturation) across simulated adult gastric and intestinal digestion using gel electrophoresis, ELISA and LC-MS. Intact LF retention across digestion was similar across LF types, but the highest iron-saturated hmLF had greater retention in the simulated gastric fluid than all other sample types. Peptides identified in digested hmLF samples strongly correlated with digested rhLF samples (0.86 < r < 0.92 in the gastric phase and 0.63 < r < 0.70 in the intestinal phase), whereas digested bLF samples were significantly different. These findings support the potential for rhLF as a food ingredient for human consumption. Full article
(This article belongs to the Special Issue Bioactive Milk Proteins and Human Health)
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<p>Experimental workflow for peptide analysis and intact protein quantitation of human, bovine and recombinant human lactoferrin across simulated digestion (INFOGEST static in vitro simulation). Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%).</p>
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<p>Relative concentration (%) of the intact hmLF, bLF and rhLF measured via ELISA of the digestive samples compared with the control. Relative concentration was calculated with the following equation: measured LF concentration in the digestive sample divided by its concentration in the control sample × 100, and it was averaged and expressed in the bar graph as the mean values ± standard deviation. Solid and pattern bars indicate the low- and high-iron-saturated samples, respectively. Differing letters indicate significant differences in the relative concentration of the intact LF among sample types (Tukey’s HSD). Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%).</p>
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<p>Gel images of the intact lactoferrin (H, hmLF and R, rhLF) and LF-derived peptides in the control (C, no digestion) and digestive samples (G, gastric; and I, intestinal) separated by Western blot. The numerical value at the end of the sample ID represents the iron saturation levels. Western blot was performed in triplicate (<b>a</b>–<b>c</b>). <sup>1</sup> Pepsin denotes the pepsin solution used for gastric digestion. <sup>2</sup> SGF <span class="html-italic">w/o</span> LF means that the gastric sample was digested without LF.</p>
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<p>Comparison of the peptides identified in each sample. Bar graph expresses (<b>a</b>) counts (the number of identified peptides) and (<b>b</b>) abundances (sum of total peak area of all peptides) of bLF, hmLF and rhLF peptides as the mean values ± standard deviation. Solid and pattern bars indicate the low- and high-iron-saturated samples, respectively. Differing letters indicate significant differences in the relative concentration of the intact LF among sample types (Tukey’s HSD). Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%).</p>
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<p>Comparison of the peptides identified in the control and digestive samples before and after iron saturation. (<b>a</b>) Venn diagram expresses the counts of the identified peptides in low- and high-iron-saturated samples, and (<b>b</b>) scatter plots show the similarities/differences between the peptides that were identified in both samples. The peptide correlations between the samples were evaluated by correlation analysis using peptide abundances expressed with the log10 scale. The Pearson correlation coefficient (r) is displayed at the top of the graph. Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%). Numbers under the peptide counts identified in common indicate the percentage of those counts that were identified as in common as calculated by the following equation: Count of the peptides in common ÷ (Counts of the unique peptides in each sample + Count of the peptides in common) × 100.</p>
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<p>Comparison of the peptides identified in both hmLF and (<b>a</b>) rhLF or (<b>b</b>) bLF samples. Scatter plots show the similarities/differences between the peptides that were identified in both samples. The peptide correlations between the samples were evaluated by correlation analysis using peptide abundances expressed with the log10 scale. The Pearson correlation coefficient (r) is displayed at the top of the graph. Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%).</p>
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<p>Heatmap and hierarchical clustering express similarities and differences between the peptide abundances (log10 scale) identified in each sample. Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%).</p>
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<p>Comparison of relative abundances (%) of bioactive peptides. Bioactivity of the identified peptides in each sample was predicted via MBPDB search, and all matched peptides were grouped based on their assigned bioactive functions (blue, ACE-inhibitory; orange, antimicrobial; red, antithrombotic; green, opioid; yellow, osteoanabolic; and gray, increase cellular growth). Sample names indicate LF type (H, human milk; R, recombinant human; and B, bovine), digestion phase (C, control; G, gastric; and I, intestinal) and iron saturation level (%).</p>
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15 pages, 1138 KiB  
Review
Revealing the Potency of Growth Factors in Bovine Colostrum
by Yalçın Mert Yalçıntaş, Hatice Duman, Jose M. Miranda López, Alicia C. Mondragón Portocarrero, Mauro Lombardo, Farid Khallouki, Wojciech Koch, Matteo Bordiga, Hesham El-Seedi, António Raposo, Jose Luiz de Brito Alves and Sercan Karav
Nutrients 2024, 16(14), 2359; https://doi.org/10.3390/nu16142359 (registering DOI) - 21 Jul 2024
Abstract
Colostrum is a nutritious milk synthesized by mammals during the postpartum period, and its rich bioactive components has led to a global increase in the consumption of bovine colostrum as a supplement. Bovine colostrum contains key components such as immunoglobulins, oligosaccharides, lactoferrin and [...] Read more.
Colostrum is a nutritious milk synthesized by mammals during the postpartum period, and its rich bioactive components has led to a global increase in the consumption of bovine colostrum as a supplement. Bovine colostrum contains key components such as immunoglobulins, oligosaccharides, lactoferrin and lysozyme. It is a special supplement source due to its natural, high bioavailability and high concentrations of growth factors. Growth factors are critical to many physiological functions, and considering its presence in the colostrum, further research must be conducted on its safe application in many bodily disorders. Growth factors contribute to wound healing, muscle and bone development, and supporting growth in children. Additionally, the molecular mechanisms have been explored, highlighting the growth factors roles in cell proliferation, tissue regeneration, and the regulation of immune responses. These findings are crucial for understanding the potential health effects of bovine colostrum, ensuring its safe use, and forming a basis for future clinical applications. This review article examines the growth factors concentration in bovine colostrum, their benefits, clinical studies, and molecular mechanisms. Full article
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<p>Growth factors in bovine colostrum [<a href="#B2-nutrients-16-02359" class="html-bibr">2</a>,<a href="#B9-nutrients-16-02359" class="html-bibr">9</a>].</p>
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<p>The molecular mechanism of the contribution of growth factors found in bovine colostrum to wound healing. Growth factors found in bovine colostrum stimulate the Ras/MAPK and PI3K/Akt signaling pathways through receptor binding, promoting the proliferation and differentiation of cells in the affected area. Consequently, the wound-healing process is accelerated [<a href="#B25-nutrients-16-02359" class="html-bibr">25</a>,<a href="#B26-nutrients-16-02359" class="html-bibr">26</a>]. (p85: regulatory subunit of phosphatidylinositol 3-kinase, p110: catalytic subunit of phosphatidylinositol 3-kinase, PTEN: phosphatase and tensin homolog, Akt: protein kinase B, PIP2: phosphatidylinositol (4,5)-bisphosphate, PIP3: phosphatidylinositol (3,4,5)-trisphosphate, TSC: tuberous sclerosis complex, Rheb: Ras homolog enriched in brain, mTORC1: mechanistic target of rapamycin complex, LKB1: liver kinase B1, AMPK1: AMP-activated protein kinase, GRB2: growth factor receptor-bound protein 2, SOS: Son of Sevenless, Ras: rat sarcoma, Raf: rapidly accelerated fibrosarcoma, MEK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase).</p>
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13 pages, 556 KiB  
Review
Is There an Ideal Diet? Some Insights from the POUNDS Lost Study
by George A. Bray, Lu Qi and Frank M. Sacks
Nutrients 2024, 16(14), 2358; https://doi.org/10.3390/nu16142358 (registering DOI) - 20 Jul 2024
Viewed by 95
Abstract
Diets for weight loss have a long history but an ideal one has not yet been clearly identified. To compare low-fat and lower carbohydrate diets, we designed The Preventing Overweight by Novel Dietary Strategies (POUNDS) Lost study. This is a 2 × 2 [...] Read more.
Diets for weight loss have a long history but an ideal one has not yet been clearly identified. To compare low-fat and lower carbohydrate diets, we designed The Preventing Overweight by Novel Dietary Strategies (POUNDS) Lost study. This is a 2 × 2 factorial study with diets of 20% or 40% fat and 15% or 25% protein with a graded carbohydrate intake of 35, 45, 55 and 65%. Weight loss, overall, was modest at nearly 6% with all four diets, and no significant dietary difference. The variability in weight loss in each diet group was significant, ranging from greater than 20% to a small weight gain. Studies of genetic variations in relation to weight loss showed that the diet that was selected could significantly affect weight loss, emphasizing that there is no ideal diet and more than one diet can be used to treat obesity. Weight loss was also influenced by the level of baseline triiodothyronine or thyroxine, and baseline carbohydrate and insulin resistance. Achieving a stable Health Eating Food Diversity Index, eating more protein, eating more fiber, engaging in more physical activity, sleeping better and eating less ultra-processed foods were beneficial strategies for weight loss in this trial. Although there is no “ideal diet”, both the DASH diet and the Mediterranean diet have clinical trials showing their significant benefit for cardiovascular risk factors. Finally, the lesson of the “Last Chance Diet”, which recommended a diet with protein from gelatin, proved that some diets could be hazardous. Full article
(This article belongs to the Special Issue Dietary Patterns and Clinical Health Outcomes)
15 pages, 811 KiB  
Review
Molecular Mechanisms of Plant Extracts in Protecting Aging Blood Vessels
by Yuxin Luo, Zeru Zhang, Weijian Zheng, Zhi Zeng, Lei Fan, Yuquan Zhao, Yixin Huang, Suizhong Cao, Shumin Yu and Liuhong Shen
Nutrients 2024, 16(14), 2357; https://doi.org/10.3390/nu16142357 (registering DOI) - 20 Jul 2024
Viewed by 92
Abstract
Plant Extracts (PE) are natural substances extracted from plants, rich in various bioactive components. Exploring the molecular mechanisms and interactions involved in the vascular protective effects of PE is beneficial for the development of further strategies to protect aging blood vessels. For this [...] Read more.
Plant Extracts (PE) are natural substances extracted from plants, rich in various bioactive components. Exploring the molecular mechanisms and interactions involved in the vascular protective effects of PE is beneficial for the development of further strategies to protect aging blood vessels. For this review, the content was obtained from scientific databases such as PubMed, China National Knowledge Infrastructure (CNKI), and Google Scholar up to July 2024, using the search terms “Plant extracts”, “oxidative stress”, “vascular aging”, “endothelial dysfunction”, “ROS”, and “inflammation”. This review highlighted the effects of PE in protecting aging blood vessels. Through pathways such as scavenging reactive oxygen species, activating antioxidant signaling pathways, enhancing respiratory chain complex activity, inhibiting mitochondrial-reactive oxygen species generation, improving nitric oxide bioavailability, downregulating the secretion of inflammatory factors, and activating sirtuins 1 and Nrf2 signaling pathways, it can improve vascular structural and functional changes caused by age-related oxidative stress, mitochondrial dysfunction, and inflammation due to aging, thereby reducing the incidence of age-related cardiovascular diseases. Full article
(This article belongs to the Section Geriatric Nutrition)
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<p>Pathways of PE protection against vascular aging. (This figure was created using BioRender).</p>
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42 pages, 2231 KiB  
Review
Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies
by Marius Emil Rusu, Galya Bigman, Alice S. Ryan and Daniela-Saveta Popa
Nutrients 2024, 16(14), 2356; https://doi.org/10.3390/nu16142356 (registering DOI) - 20 Jul 2024
Viewed by 132
Abstract
Aging is a complex process and a significant risk factor for chronic diseases. Menopause, a component of aging in women, is associated with several important cardiometabolic conditions including metabolic syndrome, osteoporosis, and cardiovascular diseases. Menopausal women could benefit from preventative strategies that may [...] Read more.
Aging is a complex process and a significant risk factor for chronic diseases. Menopause, a component of aging in women, is associated with several important cardiometabolic conditions including metabolic syndrome, osteoporosis, and cardiovascular diseases. Menopausal women could benefit from preventative strategies that may decrease morbidity and mortality and improve their quality of life. Vitamins D and K are essential nutrients required for bone health, immune function, and reducing cardiovascular risks, yet their synergistic effect is less understood in aging women. This is the first comprehensive review to summarize the evidence found in randomized clinical trials of the beneficial effects of vitamin D and K co-treatment in postmenopausal women. In our literature search across key electronic databases such as Cochrane, PubMed, and Ovid, we identified 31 pertinent studies. Overall, significant findings indicate that the combined intake of vitamins D and K may positively affect cardiovascular and bone health in postmenopausal women, emphasizing the importance of maintaining a healthy diet rich in vegetables and fermented dairy products. Given the challenges in obtaining all necessary nutrients solely through the diet, vitamin D and K supplements are recommended for postmenopausal women to promote healthy aging and well-being. Full article
(This article belongs to the Section Nutrition in Women)
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<p>Flow chart illustrating the process of selecting studies.</p>
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<p>Chemical structures of vitamin D.</p>
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<p>Chemical structures of naturally occurring vitamin K.</p>
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<p>The impact of vitD and K on VC and CVD (AGEs—advanced glycation end products; BMP-2—bone morphogenetic protein 2; CVD—cardiovascular disease; dp-cMGP—dephosphorylated–carboxylated matrix Gla protein; dp-ucMGP—dephosphorylated–uncarboxylated matrix Gla protein; Gla—γ-carboxylated glutamic acid; IL—interleukin; NF-kB—nuclear factor kappa-light-chain enhancer of activated B cells; p-cMGP—phosphorylated-carboxylated matrix Gla protein; RAGE—receptor for advanced glycation end products; TNF-α—tumor necrosis factor-alpha; VC—vascular calcification; VitD—vitamin D; VitK—vitamin K; VSMC—vascular smooth muscular cells; ↑—increase; ↓—decrease).</p>
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<p>The impact of vitamins D and K on bone mineralization (Akt—protein kinase B; ALP—alkaline phosphatase; BMD—bone mineral density; BMP-2—bone morphogenetic protein 2; cOC—carboxylated osteocalcin; IκB—inhibitor of nuclear factor kappa B; NFATc1—nuclear factor of activated T-cells 1; NF-kB—Nuclear factor kappa-light-chain enhancer of activated B cells; OPG—osteoprotegerin; PI3K—Phosphatidylinositide-3-kinase; RANKL—the receptor activator of NF-κB ligand; RUNX2—runt-related transcription factor 2; ucOC—undercarboxylated osteocalcin; VDR—vitamin D receptor; VitD—vitamin D; VitK—vitamin K; ↑—increase; ↓—decrease).</p>
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15 pages, 814 KiB  
Article
Habitual Iron Supplementation Associated with Elevated Risk of Chronic Kidney Disease in Individuals with Antihypertensive Medication
by Xiaoyan Ma, Jiali Lv, Shuai Zhang, Xiaofeng Zhang, Xia Lin, Shengxu Li, Lin Yang, Fuzhong Xue, Fan Yi and Tao Zhang
Nutrients 2024, 16(14), 2355; https://doi.org/10.3390/nu16142355 (registering DOI) - 20 Jul 2024
Viewed by 128
Abstract
The aim of this study was to examine the effects of habitual iron supplementation on the risk of CKD in individuals with different hypertensive statuses and antihypertension treatment statuses. We included a total of 427,939 participants in the UK Biobank study, who were [...] Read more.
The aim of this study was to examine the effects of habitual iron supplementation on the risk of CKD in individuals with different hypertensive statuses and antihypertension treatment statuses. We included a total of 427,939 participants in the UK Biobank study, who were free of CKD and with complete data on blood pressure at baseline. Cox proportional hazards regression models were used to examine the adjusted hazard ratios of habitual iron supplementation for CKD risk. After multivariable adjustment, habitual iron supplementation was found to be associated with a significantly higher risk of incident CKD in hypertensive participants (HR 1.12, 95% CI 1.02 to 1.22), particularly in those using antihypertensive medication (HR 1.21, 95% CI 1.08 to 1.35). In contrast, there was no significant association either in normotensive participants (HR 1.06, 95% CI 0.94 to 1.20) or in hypertensive participants without antihypertensive medication (HR 1.02, 95% CI 0.90 to 1.17). Consistently, significant multiplicative and additive interactions were observed between habitual iron supplementation and antihypertensive medication on the risk of incident CKD (p all interaction < 0.05). In conclusion, habitual iron supplementation was related to a higher risk of incident CKD among hypertensive patients, the association might be driven by the use of antihypertensive medication. Full article
(This article belongs to the Section Micronutrients and Human Health)
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<p>Flowchart of the participant inclusion in this study. Abbreviations: CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; UACR = urinary albumin–creatinine ratio; ICD-10 = the international statistical classification of diseases and related health problems 10th revision.</p>
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<p>Joint associations (HR, 95% CI) of habitual iron supplement use and hypertensive status (normotension or hypertension) as well as antihypertensive status of participants with hypertension (without medication or with medication) with chronic kidney disease incidence. Notes: Without iron indicates the participants not using iron supplements. With iron indicates the participants using iron supplements. Without medication indicates participants with hypertension not using antihypertensive medication. With medication indicates participants with hypertension using antihypertensive medication. HRs (95% CI) were adjusted for age (continuous), sex (male or female), race (White, Asian, Black, mix, or others), the Townsend deprivation index (continuous), alcohol drinking status (never drinking, former drinking, or current drinking), smoking status (never smoker, former smoker, or current smoker), vitamin supplementation (yes or no), other mineral supplementation (yes or no), physical activity (inactive, insufficient, or active), healthy diet (yes or no), BMI (continuous), anemia (yes or no), diabetes (yes or no), hypercholesterolemia (yes or no), and aspirin use (yes or no). Healthy diet was defined as at least 4 of the following 7 food groups: fruits ≥ 3 servings/day; vegetables ≥ 3 servings/day; fish ≥ 2 servings/day; processed meats ≤ 1 serving/week; unprocessed red meats ≤ 1.5 servings/week; whole grains ≥ 3 servings/day; and refined grains ≤ 1.5 servings/day.</p>
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22 pages, 2785 KiB  
Review
Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide
by Chuxiong Zheng, Yumeng Li, Xin Wu, Le Gao and Xiaoyi Chen
Nutrients 2024, 16(14), 2354; https://doi.org/10.3390/nu16142354 (registering DOI) - 20 Jul 2024
Viewed by 116
Abstract
Nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD+), is involved in the regulation of many physiological and metabolic reactions in the body. NMN can indirectly affect cellular metabolic pathways, DNA repair, and senescence, while also being essential for [...] Read more.
Nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD+), is involved in the regulation of many physiological and metabolic reactions in the body. NMN can indirectly affect cellular metabolic pathways, DNA repair, and senescence, while also being essential for maintaining tissues and dynamic metabolic equilibria, promoting healthy aging. Therefore, NMN has found many applications in the food, pharmaceutical, and cosmetics industries. At present, NMN synthesis strategies mainly include chemical synthesis and biosynthesis. Despite its potential benefits, the commercial production of NMN by organic chemistry approaches faces environmental and safety problems. With the rapid development of synthetic biology, it has become possible to construct microbial cell factories to produce NMN in a cost-effective way. In this review, we summarize the chemical and biosynthetic strategies of NMN, offering an overview of the recent research progress on host selection, chassis cell optimization, mining of key enzymes, metabolic engineering, and adaptive fermentation strategies. In addition, we also review the advances in the role of NMN in aging, metabolic diseases, and neural function. This review provides comprehensive technical guidance for the efficient biosynthesis of NMN as well as a theoretical basis for its application in the fields of food, medicine, and cosmetics. Full article
(This article belongs to the Section Nutrigenetics and Nutrigenomics)
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<p>The two N-stereoisomers of NMN.</p>
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<p>The common metabolic pathways of NAD<sup>+</sup> and NMN. There are three major biosynthetic pathways of NAD+: the Preiss–Handler path-way (blue); the de novo synthesis pathway (green); and the salvage pathway (pink).</p>
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<p>Bromoacetyl ribose method.</p>
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<p>TMSOTf catalytic condensation.</p>
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<p>AMP acid hydrolysis method.</p>
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<p>Potential benefits of NMN supplementation. As a supplemental precursor of NAD+, NMN has a modulating effect on the aging-related deterioration of physical function or diseases, including preventing cognitive decline, improving tissue and organ function, improving metabolic health, reducing inflammation, and increasing physiological benefits, which together may extend a patient’s healthy and overall lifespan.</p>
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24 pages, 1050 KiB  
Review
Saffron as a Promising Therapy for Inflammatory Bowel Disease
by Mudasir Rashid, Rumaisa Rashid, Sabtain Saroya, Mrinalini Deverapalli, Hassan Brim and Hassan Ashktorab
Nutrients 2024, 16(14), 2353; https://doi.org/10.3390/nu16142353 (registering DOI) - 20 Jul 2024
Viewed by 104
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn’s disease (CD) or ulcerative colitis (UC). Despite substantial [...] Read more.
Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn’s disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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<p>Summary of the clinical features commonly associated with CD and UC: the detailed clinical differences between CD and UC such as the location, histology, colonoscopy, stool complications, and associated conditions such as colorectal cancer. Adopted with permission from the website AMBOSS.com© (<a href="https://www.amboss.com/us/knowledge/crohn-disease" target="_blank">https://www.amboss.com/us/knowledge/crohn-disease</a>, accessed on 18 June 2024).</p>
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18 pages, 1896 KiB  
Review
Contemporary Perspectives on the Role of Vitamin D in Enhancing Gut Health and Its Implications for Preventing and Managing Intestinal Diseases
by Jiaxin Wang, Lihua Mei, Yanling Hao, Yajun Xu, Qing Yang, Zhaolai Dai, Ying Yang, Zhenlong Wu and Yun Ji
Nutrients 2024, 16(14), 2352; https://doi.org/10.3390/nu16142352 (registering DOI) - 20 Jul 2024
Viewed by 112
Abstract
Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a [...] Read more.
Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases. Full article
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<p>The synthesis, sources, and metabolism of vitamin D. Under the influence of UV-B radiation, the 7-dehydrocholesterol in the skin undergoes conversion into pre-vitamin D, subsequently transforming into vitamin D<sub>3</sub> through body temperature-mediated processes. Alternatively, dietary supplements can also serve as sources of vitamin D. Notably, vitamin D<sub>2</sub> is sourced from plants, whereas vitamin D<sub>3</sub> originates from animals. Upon entering the bloodstream, vitamin D<sub>2</sub>/D<sub>3</sub> binds to the vitamin D binding protein (DBP), facilitating its transportation to the liver and kidneys. Within these organs, it undergoes successive transformations, ultimately culminating in the formation of biologically active 1,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)D<sub>3</sub>). This active form is then circulated throughout the body via the bloodstream, delivering its vital functions to various organs and tissues. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a> (accessed on 18 July 2024).</p>
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<p>Unlocking the nexus: vitamin D, gut microbes, and epithelial cell dynamics. The vitamin D receptors (VDR) are highly abundant in intestinal epithelial cells [<a href="#B58-nutrients-16-02352" class="html-bibr">58</a>]. Following the entry of vitamin D into intestinal epithelial cells, VDR can form a heterodimer with RXR. This complex translocates to the nucleus and binds to the vitamin D response element (VDRE) in the promoter region of the target genes, thereby regulating VDR expression. Interactions between vitamin D/VDR and intestinal microbes are observed. On one hand, they enhance tight junction protein expression, maintain intestinal epithelial tissue integrity, reduce bacterial translocation, promote colonization by beneficial bacteria, and alleviate mucosal damage and abnormal immune activation [<a href="#B59-nutrients-16-02352" class="html-bibr">59</a>,<a href="#B60-nutrients-16-02352" class="html-bibr">60</a>,<a href="#B61-nutrients-16-02352" class="html-bibr">61</a>]. On the other hand, the gut microbiota can produce lithocholic acid (LCA), which facilitates vitamin D absorption. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a> (accessed on 18 July 2024).</p>
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<p>Modulation of intestinal barrier and mucosal immunity by vitamin D. Upon entering the intestine, vitamin D plays a crucial role in modulating immune responses by facilitating the differentiation of mononuclear macrophages into B cells and dendritic cells. This process significantly enhances the recognition and presentation of antigens. Furthermore, vitamin D promotes the transformation of dendritic cells into T cells, steering their differentiation towards Th2 and Treg phenotypes. This shift is accompanied by an increase in the secretion of anti-inflammatory cytokines such as IL-10 and TGF-β, while inhibiting the differentiation into pro-inflammatory Th1, Th17, and Tfh cells. Notably, vitamin D also downregulates the secretion of pro-inflammatory cytokines, including IFN, TNF-α, IL-17, and IL-6, further attenuating inflammatory responses. Additionally, it upregulates the expression of tight junction proteins such as occludin, zonula occludens (ZOs), and claudins, thereby reinforcing intestinal barrier integrity. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a> (accessed on 18 July 2024).</p>
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<p>Factors affecting gut health and the role of vitamin D in gut diseases. Various factors including genetic predisposition, environmental influences, dietary patterns, stress levels, and emotional states contribute to the development of gut-related diseases. In this context, vitamin D supplementation has emerged as a promising intervention for alleviating conditions such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease (CeD). IBD primarily manifests through colonic muscle hypertrophy, epithelial tissue fissures, pebble-like alterations (ulcerative colitis, UC), and mucosal injury (Crohn’s disease, CD). IBS patients often experience abnormal spasms in the large intestine and mucosal damage, leading to symptoms of constipation (IBS-C), diarrhea (IBS-D), or a combination of both (IBS-M). CeD, primarily affecting susceptible individuals consuming gluten, involves abnormal activation of intestinal mucosal immunity, consequently compromising the integrity of the intestinal barrier. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a> (accessed on 18 July 2024).</p>
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15 pages, 1033 KiB  
Article
Vitamin D and the Risk of Developing Hypertension in the SUN Project: A Prospective Cohort Study
by Ana Valer-Martinez, Maira Bes-Rastrollo, Jose Alfredo Martinez, Miguel Angel Martinez-Gonzalez and Carmen Sayon-Orea
Nutrients 2024, 16(14), 2351; https://doi.org/10.3390/nu16142351 (registering DOI) - 20 Jul 2024
Viewed by 119
Abstract
Vitamin D deficiency has been associated with a higher risk of multiple diseases, including cardiovascular disorders. The purpose of this study was to examine the potential association between predicted levels of serum 25(OH)D and the risk of new-onset hypertension in a large Mediterranean [...] Read more.
Vitamin D deficiency has been associated with a higher risk of multiple diseases, including cardiovascular disorders. The purpose of this study was to examine the potential association between predicted levels of serum 25(OH)D and the risk of new-onset hypertension in a large Mediterranean cohort. A validated 136-item food frequency questionnaire was used as the dietary assessment tool. 25(OH)D serum levels were predicted using a previously validated equation. We performed Cox regression models to analyze the association between predicted serum 25(OH)D and the risk of hypertension, according to quartiles of forecasted vitamin D at baseline, after adjusting for multiple potential confounders. Over a median follow-up of 12.3 years, 2338 new cases of hypertension were identified. The analyses revealed a significant inverse association between predicted serum levels of 25(OH)D at baseline and the risk of hypertension. Individuals in the highest quartile showed a 30% relatively lower risk of hypertension compared to the lowest quartile (hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.60–0.80, p-trend < 0.001). The outcomes remained significant after performing sensitivity analyses. The findings suggested that higher levels of forecasted vitamin D are inversely and independently associated with the risk of incident hypertension, implying that vitamin D may offer protective benefits against the disease. Full article
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<p>Flowchart of participants included in the analyses. <sup>a</sup> Energy limits predefined by Willett (women: &lt;500 kcal/d or &gt;3500 kcal/d; men: &lt;800 kcal/d or &gt;4000 kcal/d).</p>
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<p>Sensitivity analyses: HR and 95% CI (Q4 vs. Q1) for incident hypertension according to forecasted serum 25(OH)D status (comparison of upper versus lowest quartile). 1. Fully adjusted model for age, sex, marital status, lifetime smoking (pack years), smoking status, years at university, daily TV consumption, physical activity, weight change, adherence to Mediterranean diet score, energy intake, alcohol consumption, following a specific diet, sugar-sweetened beverage intake, vitamin D supplementation, snacking, dietary consumption of sodium, potassium, calcium, and magnesium, family history of hypertension, prevalent hypercholesterolemia, prevalent hypertriglyceridemia, use of analgesic drugs, and obesity. 2. Without prevalent hypertriglyceridemia adjustment. 3. Without prevalent hypercholesterolemia adjustment. 4. Without extreme daily energy intake (&lt;p1 or &gt;p99). 5. Without outliers located within ±1.5 interquartile range of the average of predicted vitamin D. 6. Without participants who were diagnosed of hypertension during the first 2 years of follow-up. 7. Without participants with a follow-up period of 14 years or more.</p>
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<p>Restricted cubic splines dose–response association: Adjusted HR * and 95% CI for the risk of developing hypertension according to predicted levels of serum 25(OH)D. * Adjusted for age, sex, marital status, lifetime smoking (pack years), smoking status, years at university, daily TV consumption, physical activity, weight change, adherence to Mediterranean diet score, energy intake, alcohol consumption, following a specific diet, sugar-sweetened beverage intake, vitamin D supplementation, snacking, dietary consumption of sodium, potassium, calcium, and magnesium, family history of hypertension, prevalent hypercholesterolemia, prevalent hypertriglyceridemia, use of analgesic drugs, and obesity. Red line represents HR, and dotted lines represent 95% confidence intervals.</p>
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<p>Nelson–Aalen graph: cumulative incidence of hypertension during follow-up according to predicted vitamin D status (cut-off point of 20 ng/mL). Adjusted for age, sex, marital status, lifetime smoking (pack years), smoking status, years at university, daily TV consumption, physical activity, weight change, adherence to Mediterranean diet score, energy intake, alcohol consumption, following a specific diet, sugar-sweetened beverage intake, vitamin D supplementation, snacking, dietary consumption of sodium, potassium, calcium, and magnesium, family history of hypertension, prevalent hypercholesterolemia, prevalent hypertriglyceridemia, use of analgesic drugs, and obesity.</p>
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21 pages, 4007 KiB  
Article
Juvenile/Peripubertal Exposure to Omega-3 and Environmental Enrichment Differentially Affects CORT Secretion and Adulthood Stress Coping, Sociability, and CA3 Glucocorticoid Receptor Expression in Male and Female Rats
by Julie Raymond, Alexandre Morin, Meenakshie Bradley-Garcia and Hélène Plamondon
Nutrients 2024, 16(14), 2350; https://doi.org/10.3390/nu16142350 (registering DOI) - 20 Jul 2024
Viewed by 121
Abstract
In adult rats, omega-3 supplementation through fish oil (FO) and environmental enrichment (EE) have shown beneficial effects on cognition and stress regulation. This study assessed sex-specific effects of FO and EE during adolescence, a period critical for brain maturation, on adulthood coping mechanisms, [...] Read more.
In adult rats, omega-3 supplementation through fish oil (FO) and environmental enrichment (EE) have shown beneficial effects on cognition and stress regulation. This study assessed sex-specific effects of FO and EE during adolescence, a period critical for brain maturation, on adulthood coping mechanisms, sociability, and glucocorticoid regulation. An amount of 64 Wistar rats [n = 32/sex; postnatal day (PND) 23] were assigned to supplementation of control soybean oil (CSO) or menhaden fish oil (FO; 0.3 mL/100 g) from PND28 to 47 and exposed to EE or regular cage (RC) housing from PND28 to 58, with their blood corticosterone (CORT) levels being assessed weekly. As adults, exposure to repeated forced swim tests (FSTs; PND90–91) enabled analysis of coping responses, while socioemotional and memory responses were evaluated using the OFT, EPM, SIT, and Y maze tests (PND92–94). Immunohistochemistry determined hippocampal CA1/CA3 glucocorticoid receptor (GR) expression (PND95). CORT secretion gradually increased as the supplementation period elapsed in female rats, while changes were minimal in males. Coping strategies in the FST differed between sexes, particularly in FO-fed rats, where females and males, respectively, favoured floating and tail support to minimise energy consumption and maintain immobility. In the SIT, FO/EE promoted sociability in females, while a CSO diet favoured social recognition in males. Reduced CA3 GR-ir expression was found in FO/RC and CSO/EE rat groups, supporting stress resilience and memory consolidation. Our findings support environment and dietary conditions to exert a sex-specific impact on biobehavioural responses. Full article
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<p>Timeline of the experiment. Wistar rats (male and female, <span class="html-italic">N</span> = 64) arrived at the facility at PND23. Dietary supplementation [FO or CSO] was provided daily from PND28 to 47, and rats were exposed to EE or RC from PND28 to 59. Four conditions were tested: CSO/RC, CSO/EE, FO/RC, and FO/EE. Following the FST (PND90–91), rats were exposed to the OFT, EPM, SIT and Y-Maze (PND92–94). Brain tissue was collected on PND95. <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: environmental enrichment; RC: regular cage; CORT: corticosterone; FST: forced swim test; OFT: open field test; EPM: elevated-plus maze; SIT: social interaction test; GR-ir: glucocorticoid receptors</span>.</p>
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<p>Effect of supplementation, sex, and environment in the forced swim test (FST) on time spent climbing (<b>A</b>), swimming (<b>B</b>), immobility by floating (<b>C</b>), and immobility by tail support (<b>D</b>). Increased climbing was observed for CSO/RC males compared to all groups (<span class="html-italic">p</span> &lt; 0.001; #). FO Females climbed more than CSO regardless of the environment (<span class="html-italic">p</span> &lt; 0.001; *; (<b>A</b>)). Swimming was enhanced in CSO-fed females compared to male counterparts in both RC and EE (<span class="html-italic">p</span> &lt; 0.001; &amp;). Male CSO/RC rats show reduced swim compared to all groups (<span class="html-italic">p</span> &lt; 0.01, #; (<b>B</b>)). Immobility was increased in FO/RC females compared to all groups (<span class="html-italic">p</span> &lt; 0.001; #; (<b>C</b>)). Male rats fed FO used tail support to maintain immobility (<span class="html-italic">p</span> = 0.001; &amp;), while female counterparts preferred floating (<span class="html-italic">p</span> &lt; 0.001; #; (<b>D</b>)). Data are presented as mean ± S.E.M. * and # indicate significant differences between groups at <span class="html-italic">p</span> &lt; 0.05. * indicates significant impact of supplementation only (<span class="html-italic">p</span> &lt; 0.05). <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: enriched environment; RC: regular cage</span>.</p>
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<p>Effect of supplementation, sex, and environment in the Open Field Test (OFT) for time spent in the centre (<b>A</b>), time spent in the periphery (<b>B</b>), frequency to centre (<b>C</b>), and frequency to periphery (<b>D</b>). Male rodents spent more time in the centre zone compared to females (<span class="html-italic">p</span> &lt; 0.05; #). CSO/EE males spent increased time in the centre zone (<b>A</b>), while females in the same condition spent increased time in the periphery ((<b>B</b>); <span class="html-italic">p</span> &lt; 0.05; *). Rats in the FO/RC and CSO/EE group also entered more frequently the centre (<b>C</b>) and peripheral zone (<b>D</b>) compared to the FO/EE condition (<span class="html-italic">p</span> &lt; 0.05; &amp;). Data are presented as mean ± S.E.M. * and # indicate a statistically significant difference between groups (<span class="html-italic">p</span> &lt; 0.05). * indicates significant impact of the condition (supplementation and housing only) with no effect of sex (<span class="html-italic">p</span> &lt; 0.05). <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: enriched environment; RC: regular cage</span>.</p>
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<p>Effect of supplementation, sex, and environment in the Elevated Plus Maze (EPM) for frequency in the open arm (<b>A</b>) and closed arm (<b>B</b>). FO-supplemented rats entered the open (<b>A</b>) and closed arms (<b>B</b>) less frequently than CSO-supplemented rats (<span class="html-italic">p</span> &lt; 0.001; &amp;). Data are presented as mean ± S.E.M. &amp; indicates a significant impact of the condition (supplementation only) without an influence of sex or housing at <span class="html-italic">p</span> &lt; 0.05. <span class="html-italic">FO: menhaden fish oil; CSO: control Soybean oil; EE: enriched environment; RC: regular cage</span>.</p>
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<p>Effect of supplementation, sex, and environment in the Social Interaction Test (SIT) for exploration in session 1 (<b>A</b>) and session 2 (<b>B</b>). FO/EE females spent more time interacting with S1 than the empty cup compared to CSO/EE counterparts (<span class="html-italic">p</span> &lt; 0.05; *), supporting increased sociability (<b>A</b>). FO supplementation in males reduced social recognition through reduced interaction time with S2 compared to CSO-fed counterparts (<span class="html-italic">p</span> &lt; 0.05; *), notwithstanding housing conditions (<b>B</b>). Data are presented as mean ± S.E.M. * indicates a statistically significant difference between groups at <span class="html-italic">p</span> &lt; 0.05. <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: enriched environment; RC: regular cage</span>.</p>
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<p>Effect of supplementation, sex, and environment for latency to arm re-entry (<b>A</b>) and Risk assessment behaviour (<b>B</b>) in the Y-maze passive avoidance test. In general, males CSO/RC and FO/EE took more time to re-enter the aversive arm compared to females in the same condition (<span class="html-italic">p</span> &lt; 0.05; *; (<b>A</b>)). In males, CSO/EE and FO/EE showed reduced assessments compared to the CSO/RC condition (<span class="html-italic">p</span> &lt; 0.05; *). Females underwent fewer risk assessments compared to males (<span class="html-italic">p</span> &lt; 0.05; #; (<b>B</b>)). Data are presented as mean ± S.E.M. * and # indicate a statistically significant difference between groups at <span class="html-italic">p</span> &lt; 0.05. <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: enriched environment; RC: regular cage</span>.</p>
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<p>Corticosterone levels (pg/mL) assessed on experimental DAY1, 7, 14, 21. Statistical increases in CORT were observed for all females compared to males on DAY21 (<span class="html-italic">p</span> &lt; 0.001) as well as between females from DAY1, 7, and 14 (<span class="html-italic">p</span> &lt; 0.001 for each day). Data are presented as mean ± S.E.M. * indicates a statistically significant difference between groups at <span class="html-italic">p</span> &lt; 0.05. <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: enriched environment; RC: regular cage</span>.</p>
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<p>GR-ir at the CA3 region of the hippocampus. Figure shows representative photomicrographs of GR-ir in the CA3 for each experimental condition (<b>A</b>) as well as specificity of GR antibody through superposition on Hoechst adenine–thymine-binding dye (<b>B</b>). Reduced GR-ir was observed in CSO/EE and FO/RC groups compared to CSO/RC rats (<span class="html-italic">p</span> = 0.019 and <span class="html-italic">p</span> = 0.005, respectively; (<b>C</b>)). Data are presented as mean ± S.E.M. &amp; indicates effects of supplementation and housing without effects of sex (<span class="html-italic">p</span> &lt; 0.05). <span class="html-italic">FO: menhaden fish oil; CSO: control soybean oil; EE: enriched environment; RC: regular cage; GR: glucocorticoid receptors</span>.</p>
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11 pages, 783 KiB  
Article
Post-COVID-19 Changes in Appetite—An Exploratory Study
by Georgeta Inceu, Ruben Emanuel Nechifor, Adriana Rusu, Dana Mihaela Ciobanu, Nicu Catalin Draghici, Raluca Maria Pop, Anca Elena Craciun, Mihai Porojan, Matei Negrut, Gabriela Roman, Adriana Fodor and Cornelia Bala
Nutrients 2024, 16(14), 2349; https://doi.org/10.3390/nu16142349 (registering DOI) - 20 Jul 2024
Viewed by 156
Abstract
In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 [...] Read more.
In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection. Full article
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<p>Brain regions showing significant correlations with NPY. (<b>A</b>). DC of left lingual (BA 18 L) was positively correlated with NPY value. (<b>B</b>). ReHo of left lingual (BA 37 L) was positively correlated with NPY value. NPY = neuropeptide Y; DC = degree of centrality; ReHo = regional homogeneity.</p>
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24 pages, 2872 KiB  
Article
Whole Coffee Cherry Extract Improves Working Memory and Response Inhibition: Acute and Longitudinal Results from a Remote, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
by Jennifer L. Robinson, John M. Hunter, Megan Kern, Merlina Rodas, Jasmine Jowers, Jenna Robertson and Caitlyn Wanalista
Nutrients 2024, 16(14), 2348; https://doi.org/10.3390/nu16142348 (registering DOI) - 20 Jul 2024
Viewed by 185
Abstract
Earlier laboratory-based evidence has suggested that polyphenol-rich, decaffeinated whole coffee cherry extract (CCE) supports improvements in acute and long-term cognitive performance. To better understand CCE’s potential to promote cognitive processing, we conducted a first-of-its-kind remote clinical trial. Participants were randomized into one of [...] Read more.
Earlier laboratory-based evidence has suggested that polyphenol-rich, decaffeinated whole coffee cherry extract (CCE) supports improvements in acute and long-term cognitive performance. To better understand CCE’s potential to promote cognitive processing, we conducted a first-of-its-kind remote clinical trial. Participants were randomized into one of two intervention arms: placebo or 200 mg CCE. At the beginning of the study, participants were asked to complete a set of acute cognitive challenges as part of the baseline assessment. Tasks were nearly identical to those used in previous, laboratory-based research. Acute results support that CCE outperformed placebo, reducing omissions and improving accuracy, during working memory and inhibitory control tasks. Long-term results indicate that CCE outperformed placebo on a measure of accuracy. This contributes to the literature in three ways: (1) results improve upon previously reported robust and consistent findings in a real-world setting that a single-dose of CCE acutely improved cognitive performance; (2) results replicate previous laboratory findings but in a real-world setting that long-term CCE supplementation outperformed placebo on measures of accuracy in a working memory task; and (3) it serves as proof of concept of a novel remote clinical trial model that may provide real-world evidence of efficacy while increasing accessibility and cohort diversity. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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<p>CONSORT flow chart for the remote coffee cherry clinical trial. Participants that engaged in the acute challenge are the same participants enrolled in the longitudinal study (i.e., they are not a separate pool of participants, but some participants were excluded for certain analyses based on inclusion/exclusion criteria).</p>
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<p>Depiction of participant location for the <span class="html-italic">n</span>-back and Go/No-Go tasks.</p>
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<p>Results from the acute <span class="html-italic">n</span>-back challenge.</p>
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<p>Acute results from the Go/No-Go task.</p>
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<p>Main effects of treatment from the longitudinal analysis of the <span class="html-italic">n</span>-back task. Percentages indicated are calculated from baseline. Asterisks indicate level of significance from follow-up univariate ANOVAs at each timepoint (* = <span class="html-italic">p</span> &lt; 0.05; ** = <span class="html-italic">p</span> &lt; 0.01 ).</p>
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<p>Interaction effect from the longitudinal analysis of the <span class="html-italic">n</span>-back task suggesting that CCE and placebo groups demonstrated different trajectories over time. Specifically, CCE showed a more pronounced decrease in false alarms at Day 14 and showed decreases from Day 21 to Day 28, whereas placebo did not. Percentages indicated are calculated from baseline. Asterisks indicate level of significance from follow-up univariate ANOVAs at each timepoint (* = <span class="html-italic">p</span> &lt; 0.05 ).</p>
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<p>Comparison of the acute and longitudinal results for the 1-back condition for overall proportion correct.</p>
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<p>Trend-level interaction effect from the longitudinal analysis of the <span class="html-italic">n</span>-back task suggesting that CCE and placebo groups demonstrated different trajectories over time. Specifically, CCE showed a more pronounced increase in proportion correct during the first two weeks and continued to improve, whereas placebo did not. Percentages indicated are calculated from baseline.</p>
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19 pages, 365 KiB  
Review
Organic Food in Athletes Diet—Narrative Review of Alternative Products in Sports Nutrition
by Hubert Dobrowolski, Klaudia Kopczyńska, Renata Kazimierczak, Ewa Rembiałkowska and Dariusz Włodarek
Nutrients 2024, 16(14), 2347; https://doi.org/10.3390/nu16142347 (registering DOI) - 20 Jul 2024
Viewed by 254
Abstract
Athletes are characterized by special nutritional needs. Meeting their dietary needs associated with intensive exercise is a prerequisite for effective training and success in sports competitions. Hence, it is important to supply key performance nutrients, such as macronutrients, antioxidants, calcium, vitamin D, or [...] Read more.
Athletes are characterized by special nutritional needs. Meeting their dietary needs associated with intensive exercise is a prerequisite for effective training and success in sports competitions. Hence, it is important to supply key performance nutrients, such as macronutrients, antioxidants, calcium, vitamin D, or iron, in adequate quantities. The increased need for these nutrients makes it necessary to look for food products on the market that more fully cover these needs. Such products may include organic foods. According to research, they have unique properties and are richer in selected nutrients, such as antioxidants. Hence, the aim of this review was to analyze the available literature as to whether organic foods have the potential to more fully cover the increased nutritional requirements of athletes for selected nutrients compared to conventionally produced foods. A narrative review of current literature was carried out. As the analysis showed, organic foods are characterized by a higher content of antioxidant bioactive compounds, a higher content of n-3 fatty acids, a better n:3/n:6 ratio, and a more optimal amino acid composition, which may result in an appropriate dietary ration design for athletes. In conclusion, organic food appears to be an interesting alternative to meet the special nutritional needs of professional and amateur athletes. Full article
19 pages, 6202 KiB  
Article
Ramulus Mori (Sangzhi) Alkaloids Alleviate Diabetic Nephropathy through Improving Gut Microbiota Disorder
by Wenxiu Liu, Saijun Xu, Bin Zhang and Xiaobo Sun
Nutrients 2024, 16(14), 2346; https://doi.org/10.3390/nu16142346 (registering DOI) - 20 Jul 2024
Viewed by 182
Abstract
Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori [...] Read more.
Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A. Full article
(This article belongs to the Special Issue Recent Advances in Nutrigenomics and Nutrigenetics)
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Figure 1

Figure 1
<p>The hypolipidemic and hypoglycemic effects of SZ-A in mice with DN induced by HFD and STZ. (<b>A</b>) Procedure for establishment of DN model and administration of SZA. (<b>B</b>) Serum TG levels. (<b>C</b>) Serum TCH levels. (<b>D</b>) Blood glucose levels. The data represent the mean ± SD. n = 6, ### <span class="html-italic">p</span> &lt; 0.001 versus the control group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 versus the model group.</p>
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<p>The renoprotection effects of SZ-A in HFD and STZ-induced mice. (<b>A</b>) Representative images of hematoxylin–eosin (H&amp;E) staining of kidney tissue sections from each group (scale bar: 50 μm). (<b>B</b>) Representative images of PAS staining of kidney tissue sections from each group (scale bar: 50 μm). (<b>C</b>) Kidney weight, n = 9–10. (<b>D</b>) Urine microalbumin content, n = 9–10. (<b>E</b>–<b>H</b>) Serum biochemical indexes of mice, n = 9–10. (<b>I</b>,<b>J</b>) Representative electron microscopy images of mouse glomerulus from each group (scale bars: 20 μm and 4 μm) and TEM quantification of GBM thickness, n = 6. (<b>K</b>) Representative electron microscopy images of kidney tissue mitochondria from each group (scale bar: 10 μm). The data represent the mean ± SD. # <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001 versus the control group; ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 versus the model group.</p>
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<p>16S rRNA sequencing analysis results of SZ-A-treated DN mice. (<b>A</b>) Alpha diversity analysis (the Chao1 index) between groups. (<b>B</b>) Alpha diversity analysis (the Shannon index) between groups. (<b>C</b>) Principal coordinate analysis (PCoA) diagram of transcriptional profiling of the mouse cecal contents. (<b>D</b>) Correlation analysis between gut microbiota and biochemical indicators. (<b>E</b>,<b>F</b>) Relative abundance of the bacterial altered with SZ-A treatment at the genera level. The data represent the mean ± SD. n = 5–6, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Non-targeted metabolomics analysis results of SZ-A-treated DN mice. (<b>A</b>) Partial least-squares discriminant analysis (PLS-DA) of metabolic profiles between groups (model group: n = 6; SZ-A group: n = 4). (<b>B</b>) Clustering analysis (bray-curtis distance) of metabolic profiles between groups (model group: n = 6; SZ-A group: n = 4). (<b>C</b>) Clustering heat maps and correlation analysis between differential metabolites, red indicates positive correlation and blue indicates negative correlation, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001. (<b>D</b>) The levels of metabolites between groups. Blue plot points represent down-regulated metabolites in the SZ-A group compared to the model group with statistical significance, while red plot points represent up-regulated metabolites with statistical significance.</p>
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<p>Correlation analysis of gut microbiota, serum metabolites, and biochemical indicators. (<b>A</b>,<b>B</b>) The Sankey diagrams of the combined analysis of 16sRNA sequencing and untargeted metabolomics. Each number corresponds to a metabolite.</p>
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<p>The fecal microbiota transplantation experiment mitigates metabolic disorders in HFD and STZ-induced mice. (<b>A</b>) Procedure for antibiotic pretreatment and fecal microbiota transplantation. (<b>B</b>) Blood glucose levels. (<b>C</b>) Serum TG levels. (<b>D</b>) Serum TCH levels. (<b>E</b>) Serum HDL levels. (<b>F</b>) Serum LDL levels. The data represent the mean ± SD. n = 6, # <span class="html-italic">p</span> &lt; 0.05, ### <span class="html-italic">p</span> &lt; 0.001 versus the C + FMT-PBS group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 versus the M + FMT-PBS group; <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.001 versus the M + FMT-M group; ns, not significant.</p>
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<p>The renoprotection effects of SZ-A were transferable by gut microbiota in HFD and STZ-induced mice. (<b>A</b>) Ratio of kidney weight to body weight, n = 6. (<b>B</b>) Representative images of hematoxylin–eosin (H&amp;E) staining of kidney tissue sections from each group (scale bars: 200 μm and 50 μm). (<b>C</b>) Representative images of PAS staining of kidney tissue sections from each group (scale bars: 200 μm and 50 μm). (<b>D</b>) UAlb content, n = 6. (<b>E</b>–<b>H</b>) Serum biochemical indexes of mice, n = 5–6. (<b>I</b>,<b>J</b>) Representative electron microscopy images of mouse glomerulus from each group (scale bars: 20 μm and 4 μm) and TEM quantification of GBM thickness, n = 6. (<b>K</b>) Representative electron microscopy images of kidney tissue mitochondria from each group (scale bar: 10 μm). The data represent the mean ± SD. # <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001 versus the C + FMT-PBS group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 versus the M + FMT-PBS group; <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.001 versus the M + FMT-M group; ns, not significant.</p>
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<p>Pentadecanoic acid restored podocyte injury induced by AGEs. (<b>A</b>) Cytotoxicity of pentadecanoic acid, n = 6. (<b>B</b>) The survival rate of MPC5 cells induced by AGEs under different concentrations of pentadecanoic acid, n = 5. (<b>C</b>,<b>D</b>) Representative TUNEL staining images of MPC5 cells (scale bar: 20 μm) and quantification of apoptosis, n = 6. The data represent the mean ± SD. ### <span class="html-italic">p</span> &lt; 0.001; ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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